Pain medicine training resources: Module 5

Abstract
Many pain conditions in patients tend to co-occur, influencing the clinical expressions of each other in various ways. This paper summarizes the main concurrent pain conditions by analyzing the major interactions observed. In particular, co-occurrence will be examined in: visceral pain (especially ischemic heart disease, irritable bowel syndrome, dysmenorrhea/endometriosis and urinary pain), fibromyalgia, musculoskeletal pain and headache. Two concurrent visceral pains from internal organs sharing at least part of their central sensory projection can give rise to viscero-visceral hyperalgesia, i.e., enhancement of typical pain symptoms from both districts. Visceral pain, headache and musculoskeletal pains (myofascial pain from trigger points, joint pain) can enhance pain and hyperalgesia from fibromyalgia. Myofascial pain from trigger points can perpetuate pain symptoms from visceral pain conditions and trigger migraine attacks when located in the referred pain area from an internal organ or in cervico-facial areas, respectively. The pathophysiology of these pain associations is complex and probably multifactorial; among the possible processes underlying the mutual influence of symptoms recorded in the associations is modulation of central sensitization phenomena by nociceptive inputs from one or the other condition. A strong message in these pain syndrome co-occurrence is that effective treatment of one of the conditions can also improve symptoms from the other, thus suggesting a systematic and thorough evaluation of the pain patient for a global effective management of his/her suffering.

Abstract
Chronic pelvic pain affects both men and women; there are probably common mechanisms that involve the central nervous system. In many cases, the symptoms may be localised to a single end organ. However, the involvement of the central nervous system may result in a complex regional pain syndrome affecting the whole pelvis and as a consequence, multiple-organ symptomatology. The initial trigger may be relatively benign but a predisposed individual may develop a range of significant sensory and efferent functional abnormalities. Stimuli not normally reaching threshold may be perceived and normal sensations may be magnified to become dysphoric or painful. Problems of emptying viscera and maintaining continence may occur. Significant musculoskeletal disability may arise as well as abnormalities of the autonomic nervous system. There is an association with systemic disorders. Also, psychological, behavioural, sexual and social problems arise. In the chronic pelvic pain syndromes, treatment of the end organ has a limited role, and multidisciplinary as well as interdisciplinary management is essential.

Abstract
The fear-avoidance model is an attempt to underscore the importance of cognitive and behavioral factors, in a chain of events linking pain to disability. However, it is not clear at what time point the psychological variables within the model begin to be prominent. The aim of this study was to investigate the role of these psychological variables in the development of a chronic musculoskeletal pain problem. Three stages of chronicity, defined by duration of pain, provided a proxy for the developmental process: <1 year (N=48), 1-3 years (N=47) and >3 years (N=89). Subjects completed questionnaires on fear of movement, catastrophizing, depression, pain and function. The results indicate that the relationship between fear of movement and function is moderated by the stage of chronicity. Regression analyses showed that fear of movement did not explain any variance in the group with pain duration <1 year. Fear of movement did explain variance in the groups with pain duration of 1-3 years and >3 years. This suggests that the time point in the development of a musculoskeletal pain problem might be an essential aspect of the importance of the relationship between psychological components and function.

Abstract
Background: Women scheduled to undergo hysterectomy for benign indications frequently have preoperative pelvic pain, but it is largely unknown why pain in some cases persists or even develops after surgery. This nationwide questionnaire and database study describes pain and identifies risk factors for chronic postsurgical pain 1 yr after hysterectomy for benign indications.

Methods: A pain questionnaire was mailed to 1,299 women 1 yr after hysterectomy. The response rate was 90.3%, and the presence of persistent pain was correlated to indication for surgery, surgical procedure, type of anesthesia, and other perioperative data.

Results: Pain was reported by 31.9% 1 yr after hysterectomy (chronic pain), and 13.7% had pain more than 2 days a week. Pain was not present before surgery in 14.9% of women with chronic postsurgical pain. Risk factors for chronic pain were preoperative pelvic pain (odds ratio [OR], 3.25; 95% confidence interval [CI], 2.40-4.41), previous cesarean delivery (OR, 1.54; CI, 1.06-2.26), pain as the main indication for surgery (OR, 2.98; CI, 1.54-5.77), and pain problems elsewhere (OR, 3.19; CI, 2.29-4.44). Vaginal hysterectomy versus total abdominal hysterectomy was not significantly associated with a lower risk of chronic pain (OR, 0.70; CI, 0.46-1.06). Importantly, spinal versus general anesthesia was associated with less chronic pain (OR, 0.42; CI, 0.21-0.85).

Conclusions: Thirty-two percent had chronic pain after hysterectomy, and risk factors were comparable to those seen in other operations. Interestingly, spinal anesthesia was associated with a lower frequency of chronic pain, justifying prospective study of spinal anesthesia for patients with a high risk for development of chronic postsurgical pain.

Abstract
Background: This overview reports on interventions for pain relief and for subfertility in pre-menopausal women with clinically diagnosed endometriosis.

Objectives: The objective of this overview was to summarise the evidence from Cochrane systematic reviews on treatment options for women with pain or subfertility associated with endometriosis.

Methods: Published Cochrane systematic reviews reporting pain or fertility outcomes in women with clinically diagnosed endometriosis were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation (protocols and titles) for future inclusion. The reviews, protocols and titles were identified by searching the Cochrane Database of Systematic Reviews and Archie (the Cochrane information management system) in March 2014.Pain-related outcomes of the overview were pain relief, clinical improvement or resolution and pain recurrence. Fertility-related outcomes were live birth, clinical pregnancy, ongoing pregnancy, miscarriage and adverse events.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed using the AMSTAR tool. The quality of the evidence for each outcome was assessed using GRADE methods. Review findings were summarised in the text and the data for each outcome were reported in 'Additional tables'.

Main results: Seventeen systematic reviews published in The Cochrane Library were included. All the reviews were high quality. The quality of the evidence for specific comparisons ranged from very low to moderate. Limitations in the evidence included risk of bias in the primary studies, inconsistency between the studies, and imprecision in effect estimates. Pain relief (14 reviews) Gonadotrophin-releasing hormone (GnRH) analogues One systematic review reported low quality evidence of an overall benefit for GnRH analogues compared with placebo or no treatment. Ovulation suppression Five systematic reviews reported on medical treatment using ovulation suppression. There was moderate quality evidence that the levonorgestrel-releasing intrauterine system (LNG-IUD) was more effective than expectant management, and very low quality evidence that danazol was more effective than placebo. There was no consistent evidence of a difference in effectiveness between oral contraceptives and goserelin, estrogen plus progestogen and placebo, or progestogens and placebo, though in all cases the relevant evidence was of low or very low quality. Non-steroidal anti-inflammatory drugs (NSAIDS)A review of NSAIDs reported inconclusive evidence of a benefit in symptom relief compared with placebo. Surgical interventions There were two reviews of surgical interventions. One reported moderate quality evidence of a benefit in pain relief following laparoscopic surgery compared to diagnostic laparoscopy only. The other reported very low quality evidence that recurrence rates of endometriomata were lower after excisional surgery than after ablative surgery. Post-surgical medical interventions Two reviews reported on post-surgical medical interventions. Neither found evidence of an effect on pain outcomes, though in both cases the evidence was of low or very low quality. Alternative medicine There were two systematic reviews of alternative medicine. One reported evidence of a benefit from auricular acupuncture compared to Chinese herbal medicine, and the other reported no evidence of a difference between Chinese herbal medicine and danazol. In both cases the evidence was of low or very low quality. Anti-TNF-α drugs One review found no evidence of a difference in effectiveness between anti-TNF-α drugs and placebo. However, the evidence was of low quality. Reviews reporting fertility outcomes (8 reviews) Medical interventions Four reviews reported on medical interventions for improving fertility in women with endometriosis. One compared three months of GnRH agonists with a control in women undergoing assisted reproduction and found very low quality evidence of an increase in clinical pregnancies in the treatment group. There was no evidence of a difference in effectiveness between the interventions in the other three reviews, which compared GnRH agonists versus antagonists, ovulation suppression versus placebo or no treatment, and pre-surgical medical therapy versus surgery alone. In all cases the evidence was of low or very low quality. Surgical interventions Three reviews reported on surgical interventions. There was moderate quality evidence that both live births or ongoing pregnancy rates and clinical pregnancy rates were higher after laparoscopic surgery than after diagnostic laparoscopy alone. There was low quality evidence of no difference in effectiveness between surgery and expectant management for endometrioma. One review found low quality evidence that excisional surgery resulted in higher clinical pregnancy rates than drainage or ablation of endometriomata. Post-surgical interventions Two reviews reported on post-surgical medical interventions. They found no evidence of an effect on clinical pregnancy rates. The evidence was of low or very low quality. Alternative medicine A review of Chinese herbal medicine in comparison with gestrinone found no evidence of a difference between the groups in clinical pregnancy rates. However, the evidence was of low quality. Adverse events Reviews of GnRH analogues and of danazol reported that the interventions were associated with higher rates of adverse effects than placebo; and depot progestagens were associated with higher rates of adverse events than other treatments. Chinese herbal medicine was associated with fewer side effects than gestrinone or danazol.Three reviews reported miscarriage as an outcome. No difference was found between surgical and diagnostic laparoscopy, between GnRH agonists and antagonists, or between aspiration of endometrioma and expectant management. However, in all cases the quality of the evidence was of low quality.

Authors' conclusions: For women with pain and endometriosis, suppression of menstrual cycles with gonadotrophin-releasing hormone (GnRH) analogues, the levonorgestrel-releasing intrauterine system (LNG-IUD) and danazol were beneficial interventions. Laparoscopic treatment of endometriosis and excision of endometriomata were also associated with improvements in pain. The evidence on NSAIDs was inconclusive. There was no evidence of benefit with post-surgical medical treatment.In women with endometriosis undergoing assisted reproduction, three months of treatment with GnRH agonist improved pregnancy rates. Excisional surgery improved spontaneous pregnancy rates in the nine to 12 months after surgery compared to ablative surgery. Laparoscopic surgery improved live birth and pregnancy rates compared to diagnostic laparoscopy alone. There was no evidence that medical treatment improved clinical pregnancy rates.Evidence on harms was scanty, but GnRH analogues, danazol and depot progestagens were associated with higher rates than other interventions.

Abstract
This study aims to review the use of sacral neuromodulation in the patient population with painful bladder syndrome/interstitial cystitis (PBS/IC), chronic pelvic pain (CPP), and sexual dysfunction. A literature review of the current research was carried out. This article highlights the current research findings and uses of sacral neuromodulation in patients with PBS/IC, CPP, vulvar vestibulitis, and erectile dysfunction. Current research on sacral neuromodulation on the abovementioned patient population has shown potential efficacy in pilot studies, though larger, multi-centered trials with long-term follow-up are needed.

Abstract
The prevalence and cost of chronic pain is a major physical and mental health care problem in the United States today. As a result, there has been a recent explosion of research on chronic pain, with significant advances in better understanding its etiology, assessment, and treatment. The purpose of the present article is to provide a review of the most noteworthy developments in the field. The biopsychosocial model is now widely accepted as the most heuristic approach to chronic pain. With this model in mind, a review of the basic neuroscience processes of pain (the bio part of biopsychosocial), as well as the psychosocial factors, is presented. This spans research on how psychological and social factors can interact with brain processes to influence health and illness as well as on the development of new technologies, such as brain imaging, that provide new insights into brain-pain mechanisms.

Abstract
Although interest in descending modulation of spinal cord function dates back to the time of Sherrington, the modern era began in the late 1960s when it was shown that focal electrical stimulation in the midbrain of the rat produced analgesia sufficient to permit surgery. From this report evolved the concept of endogenous systems of pain modulation. Initial interest focused on descending inhibition of spinal nociceptive processing, but we now know that descending modulation of spinal nociceptive processing can be either inhibitory or facilitatory. As our understanding of descending facilitatory, or pro-nociceptive influences grows, so too has our appreciation of its potential importance. Accumulating evidence suggests that descending facilitatory influences may contribute to the development and maintenance of hyperalgesia and thus contribute to chronic pain states.

Abstract
Chronic pelvic pain (CPP) is complex and often resistant to treatment. While the exact pathophysiology is unknown, the pain states resultant from conditions such as interstitial cystitis and the like yield patients with a presentation that bears a striking similarity to neuropathic syndromes that are known to respond to neuromodulation. While there has been past success using the sacral region as a target for spinal cord stimulation (SCS) to treat these patients, there remains to be a consensus on the optimal location for lead placement. In this article, the authors discuss the potential etiology of CPP, examine the current literature on lead placement for SCS as a method of treatment, as well as present several cases where novel lead placement was successfully employed.

Abstract
Background and objectives: Spinal cord stimulation (SCS) may reduce pain scores and improve function in patients with various chronic abdominal pain syndromes including chronic pancreatitis. Here described is a large clinical experience in SCS for severe chronic pancreatitis.

Methods: SCS was trialed in 30 patients with chronic pancreatitis. SCS trials lasted 7-14 days (median 9 days). SCS lead tips were mostly positioned at the T5 (N= 10) or T6 (N= 10) vertebral level.

Results: Twenty-four patients (80%) reported at least 50% pain relief on completion of the trial. Among these, pre-trial visual analog scale (VAS) pain scores averaged 8 ± 1.6 (standard deviation) and opioid use averaged 165 ± 120 mg morphine sulfate equivalents. During the trial, VAS pain scores decreased to 3.67 ± 2 cm (p < 0.001, Mann-Whitney Rank Sum Test) and opioid use decreased to 105 ± 101 mg morphine equivalent a day. Six patients failed the trial; one was lost to follow-up; in three patients after the implantation, the system had to be removed due to infection or lead migration; and 20 were followed for the whole year. For 20 patients followed for the whole year, VAS pain scores remained low (3.6 ± 2 cm; p < 0.001) at one year, as did opioid use (48.6 ± 58 mg morphine equivalents).

Conclusions: SCS may be a useful therapeutic option for patients with severe visceral pain from chronic pancreatitis. Prospective trial is warranted.

Abstract
Chronically painful conditions are frequently associated with sleep disturbances, i.e. changes in sleep continuity and sleep architecture as well as increased sleepiness during daytime. A new hypothesis, which has attracted more and more attention, is that disturbances of sleep cause or modulate acute and chronic pain. Since it is well-known that pain disturbs sleep the relationship between the two has since recently been seen as reciprocal. To fathom the causal direction from sleep to pain we have reviewed experimental human and animal studies on the effects of sleep deprivation on pain processing. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can interfere with analgesic treatments involving opioidergic and serotoninergic mechanisms of action. The still existing inconsistency of the human data and the exclusive focus on REM sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity.

Abstract
Abdominal pain is associated with many gastrointestinal dysfunctions, such as irritable bowel syndrome (IBS), functional dyspepsia, and inflammatory bowel disease (IBD). Visceral hypersensitivity is a key reason for development of abdominal pain that presents in these gastrointestinal disorders/diseases. The pathogenesis of visceral hypersensitivity is complex and still far from being fully understood. In animal studies, visceral hypersensitivity has been linked to several early-life adverse (ELA) events. In humans, IBD, functional dyspepsia, and IBS can have adult onset, though the adverse events that lead to visceral hypersensitivity are largely uncharacterized. In this issue of the journal, Aguirre et al. report the interesting finding that epigenetics underlies the effects of ELA events on visceral hypersensitivity. This mini-review examines models of ELA events leading to visceral hypersensitivity and the potential role of epigenetics, as reported by Aguirre et al. and others.

Available to purchase as a Kindle e-book.

Abstract
Clinical observations of viscerovisceral referred pain in patients with gastrointestinal and genitourinary disorders suggest an overlap of neurohumoral mechanisms underlying both bowel and urinary bladder dysfunctions. Close proximity of visceral organs within the abdominal cavity complicates identification of the exact source of chronic pelvic pain, where it originates, and how it relocates with time. Cross-sensitization among pelvic structures may contribute to chronic pelvic pain of unknown etiology and involves convergent neural pathways of noxious stimulus transmission from two or more organs. Convergence of sensory information from discrete pelvic structures occurs at different levels of nervous system hierarchy including dorsal root ganglia, the spinal cord and the brain. The cell bodies of sensory neurons projecting to the colon, urinary bladder and male/female reproductive organs express a wide range of membrane receptors and synthesize many neurotransmitters and regulatory peptides. These substances are released from nerve terminals following enhanced neuronal excitability and may lead to the occurrence of neurogenic inflammation in the pelvis. Multiple factors including inflammation, nerve injury, ischemia, peripheral hyperalgesia, metabolic disorders and other pathological conditions dramatically alter the function of directly affected pelvic structures as well as organs located next to a damaged domain. Defining precise mechanisms of viscerovisceral cross-sensitization would have implications for the development of effective pharmacological therapies for the treatment of functional disorders with chronic pelvic pain such as irritable bowel syndrome and painful bladder syndrome. The complexity of overlapping neural pathways and possible mechanisms underlying pelvic organ crosstalk are analyzed in this review at both systemic and cellular levels.

Abstract
Introduction and hypothesis: Interstitial cystitis is a multifaceted medical condition consisting of pelvic pain, urgency, and frequency. Can sacral neuromodulation be successfully utilized for the medium term of ≥ 6 years in interstitial cystitis patients for whom standard drug therapies have failed?

Methods: In our observational, retrospective, case-controlled review (January 2002-March 2004), we sought to discern whether neuromodulation could be successfully implemented with acceptable morbidity rates in interstitial cystitis patients. Thirty-four female patients underwent stage 1 and 2 InterStim placements under a general anesthetic. Simple means and medians were analyzed.

Results: Mean pre-op/post-op pelvic pain and urgency/frequency scores were 21.61 ± 8.6/9.22 ± 6.6 (p < 0.01), and mean pre-op/post-op visual analog pain scale (VAPS) were 6.5 ± 2.9/2.4 ± 1.1 (p < 0.01). Median age was 41 ± 14.8 years with a mean follow-up of 86 ± 9.8 months.

Conclusions: With a minimum 6-year follow-up we determined that sacral neuromodulation provides adequate improvement for the symptoms of recalcitrant interstitial cystitis.

Abstract
Aim: The aim of the study was to evaluate the efficacy of sacral nerve modulation for chronic pelvic pain after pelvic or anal surgery for benign disease.

Method: From January 2004 to December 2009, 17 (14 female; age 56 years) consecutive patients suffering from chronic pelvic pain underwent evaluation for sacral nerve modulation in three pelvic floor units.

Results: The previous surgery included stapled transanal rectal resection (five), hysterectomy (four), haemorrhoidectomy (two), stapled haemorrhoidopexy (one), fistulectomy (one), urethral sphincterotomy (one), appendicectomy (one), discectomy (one) and laparoscopy for endometriosis (one). Eight (47%) patients fulfilled the criteria for definitive implantation and were followed for a mean of 39 months. Using a visual analog pain score, pain levels fell from 8.2 preoperatively to 1.9, 2.1, 2.0 and 1.8 at 6, 12, 24 and 36 months, respectively. Age < 60 years and duration of symptoms of < 24 months were good predictors and stapling was a poor predictor of success.

Conclusion: Sacral nerve modulation seems to be effective over time in some patients with chronic pain related to previous surgery.

Abdominal and Pelvic Pain integrates basic science and clinical phenotypes into a multidisciplinary continuum of care, encouraging improved national and international standards of management. More than 45 contributors provide clear discussions of management strategies; multidisciplinary teamwork; somatic and psychological aspects of pain; pharmacotherapy, physiotherapy, psychology, and neuromodulation; and much more.

Abstract
Background: Chronic postoperative pain is a well-recognized problem after various types of surgery such as amputation, thoracotomy, mastectomy, gallbladder surgery and inguinal hernia repair. However, little is known about chronic pain after gynaecologic surgery. Therefore, the aim was to study the incidence of chronic pain after Caesarean section.

Methods: A questionnaire was sent in February/March 2003 to 244 consecutive patients who underwent Caesarean section in a one-year period from 1 October 2001 to 30 September 2002. Patients were asked about duration of postoperative abdominal scar pain, and if pain was still present to describe the frequency and intensity of pain and its impact on daily life. The questionnaire also included questions about the Caesarean section and about pain problems elsewhere.

Results: A total of 220 patients (90.2%) answered the questionnaire. The mean follow-up time was 10.2 months (range 6-17.6). Postoperative pain resolved in most patients within 3 months but 27 patients (12.3%) still had pain at the time of the interview. No patients had constant pain, but in 13 of 27 patients (5.9%) pain was present daily or almost daily. Patients with persistent pain (n = 27) had more often undergone general than spinal anaesthesia for the Caesarean section. Frequencies of pain problems elsewhere and recalls of severe acute postoperative pain were also higher among patients with persistent pain.

Conclusion: Chronic pain after Caesarean section seems to be a significant problem in at least 5.9% of patients.

Abstract
Background: Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity.

Objectives: To evaluate the efficacy, effectiveness, adverse events, and cost-effectiveness of implanted spinal neuromodulation interventions for people with chronic pain.

Search methods: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, Web of Science (ISI), Health Technology Assessments, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry from inception to September 2021 without language restrictions, searched the reference lists of included studies and contacted experts in the field.

Selection criteria: We included randomised controlled trials (RCTs) comparing SNMD interventions with placebo (sham) stimulation, no treatment or usual care; or comparing SNMD interventions + another treatment versus that treatment alone. We included participants ≥ 18 years old with non-cancer and non-ischaemic pain of longer than three months duration. Primary outcomes were pain intensity and adverse events. Secondary outcomes were disability, analgesic medication use, health-related quality of life (HRQoL) and health economic outcomes.

Data collection and analysis: Two review authors independently screened database searches to determine inclusion, extracted data and evaluated risk of bias for prespecified results using the Risk of Bias 2.0 tool. Outcomes were evaluated at short- (≤ one month), medium- four to eight months) and long-term (≥12 months). Where possible we conducted meta-analyses. We used the GRADE system to assess the certainty of evidence.

Main results: We included 15 unique published studies that randomised 908 participants, and 20 unique ongoing studies. All studies evaluated SCS. We found no eligible published studies of DRGS and no studies comparing SCS with no treatment or usual care. We rated all results evaluated as being at high risk of bias overall. For all comparisons and outcomes where we found evidence, we graded the certainty of the evidence as low or very low, downgraded due to limitations of studies, imprecision and in some cases, inconsistency. Active stimulation versus placebo SCS versus placebo (sham) Results were only available at short-term follow-up for this comparison. Pain intensity Six studies (N = 164) demonstrated a small effect in favour of SCS at short-term follow-up (0 to 100 scale, higher scores = worse pain, mean difference (MD) -8.73, 95% confidence interval (CI) -15.67 to -1.78, very low certainty). The point estimate falls below our predetermined threshold for a clinically important effect (≥10 points). No studies reported the proportion of participants experiencing 30% or 50% pain relief for this comparison. Adverse events (AEs) The quality and inconsistency of adverse event reporting in these studies precluded formal analysis. Active stimulation + other intervention versus other intervention alone SCS + other intervention versus other intervention alone (open-label studies) Pain intensity Mean difference Three studies (N = 303) demonstrated a potentially clinically important mean difference in favour of SCS of -37.41 at short term (95% CI -46.39 to -28.42, very low certainty), and medium-term follow-up (5 studies, 635 participants, MD -31.22 95% CI -47.34 to -15.10 low-certainty), and no clear evidence for an effect of SCS at long-term follow-up (1 study, 44 participants, MD -7 (95% CI -24.76 to 10.76, very low-certainty). Proportion of participants reporting ≥50% pain relief We found an effect in favour of SCS at short-term (2 studies, N = 249, RR 15.90, 95% CI 6.70 to 37.74, I2 0% ; risk difference (RD) 0.65 (95% CI 0.57 to 0.74, very low certainty), medium term (5 studies, N = 597, RR 7.08, 95 %CI 3.40 to 14.71, I2 = 43%; RD 0.43, 95% CI 0.14 to 0.73, low-certainty evidence), and long term (1 study, N = 87, RR 15.15, 95% CI 2.11 to 108.91 ; RD 0.35, 95% CI 0.2 to 0.49, very low certainty) follow-up. Adverse events (AEs) Device related No studies specifically reported device-related adverse events at short-term follow-up. At medium-term follow-up, the incidence of lead failure/displacement (3 studies N = 330) ranged from 0.9 to 14% (RD 0.04, 95% CI -0.04 to 0.11, I2 64%, very low certainty). The incidence of infection (4 studies, N = 548) ranged from 3 to 7% (RD 0.04, 95%CI 0.01, 0.07, I2 0%, very low certainty). The incidence of reoperation/reimplantation (4 studies, N =5 48) ranged from 2% to 31% (RD 0.11, 95% CI 0.02 to 0.21, I2 86%, very low certainty). One study (N = 44) reported a 55% incidence of lead failure/displacement (RD 0.55, 95% CI 0.35, 0 to 75, very low certainty), and a 94% incidence of reoperation/reimplantation (RD 0.94, 95% CI 0.80 to 1.07, very low certainty) at five-year follow-up. No studies provided data on infection rates at long-term follow-up. We found reports of some serious adverse events as a result of the intervention. These included autonomic neuropathy, prolonged hospitalisation, prolonged monoparesis, pulmonary oedema, wound infection, device extrusion and one death resulting from subdural haematoma. Other No studies reported the incidence of other adverse events at short-term follow-up. We found no clear evidence of a difference in otherAEs at medium-term (2 studies, N = 278, RD -0.05, 95% CI -0.16 to 0.06, I2 0%) or long term (1 study, N = 100, RD -0.17, 95% CI -0.37 to 0.02) follow-up. Very limited evidence suggested that SCS increases healthcare costs. It was not clear whether SCS was cost-effective.

Authors' conclusions: We found very low-certainty evidence that SCS may not provide clinically important benefits on pain intensity compared to placebo stimulation. We found low- to very low-certainty evidence that SNMD interventions may provide clinically important benefits for pain intensity when added to conventional medical management or physical therapy. SCS is associated with complications including infection, electrode lead failure/migration and a need for reoperation/re-implantation. The level of certainty regarding the size of those risks is very low. SNMD may lead to serious adverse events, including death. We found no evidence to support or refute the use of DRGS for chronic pain.

Abstract
Background: Chronic bacterial prostatitis (CBP) is frequently diagnosed in men of fertile age, and is characterized by a disabling array of symptoms, including pain in the pelvic area (for example, perineum, testicles), voiding symptoms (increased frequency and urgency, also at night; pain or discomfort at micturition), and sexual dysfunction. Cure of CBP can be attempted by long-term therapy with antibacterial agents, but relapses are frequent. Few antibacterial agents are able to distribute to the prostatic tissue and achieve sufficient concentrations at the site of infection. These agents include fluoroquinolones, macrolides, tetracyclines and trimethoprim. After the introduction of fluoroquinolones into clinical practice, a number of studies have been performed to optimize the antimicrobial treatment of CBP, and to improve eradication rates and symptom relief.

Objectives: To assess and compare the efficacy and harm of antimicrobial treatments for chronic bacterial prostatitis.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, other national or international databases and abstracts from conference proceedings on 8 August 2012.

Selection criteria: We included all randomized controlled comparisons of one antimicrobial agent versus placebo or one or more comparator antimicrobial agents, combined or not with non-antimicrobial drugs. We also included trials comparing different doses, treatment durations, dosing frequencies, or routes of administration of antimicrobial agents. We excluded studies in which patients were not diagnosed according to internationally recommended criteria, or were not subjected to lower urinary tract segmented tests.

Data collection and analysis: Study data were extracted independently by two review authors. Study outcomes were microbiological efficacy (pathogen eradication), clinical efficacy (symptom cure or improvement, or symptom scores) at test-of-cure visits or at follow-up, or both, and adverse effects of therapy. Secondary outcomes included microbiological recurrence rates.Statistical analysis was performed using a fixed-effect model for microbiological outcomes and a random-effects model for clinical outcomes and adverse effects. The results were expressed as risk ratios for dichotomous outcomes (with 95% confidence intervals) or as standardized mean differences for continuous or non-dichotomous variables.

Main results: We identified 18 studies, enrolling a total of 2196 randomized patients. The oral fluoroquinolones ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin and prulifloxacin were compared. There were no significant differences in clinical or microbiological efficacy or in the rate of adverse effects between these fluoroquinolones. In chlamydial prostatitis, (i) azithromycin showed improved eradication rates and clinical cure rates compared to ciprofloxacin, with no significant differences regarding adverse effects; (ii) azithromycin was equivalent to clarithromycin, both microbiologically and clinically; (iii) prulifloxacin appeared to improve clinical symptoms, but not eradication rates, compared to doxycycline. In ureaplasmal prostatitis, the comparisons ofloxacin versus minocycline and azithromycin versus doxycycline showed similar microbiological, clinical and toxicity profiles.

Authors' conclusions: The microbiological and clinical efficacy, as well as the adverse effect profile, of different oral fluoroquinolones are comparable. No conclusions can be drawn regarding the optimal treatment duration of fluoroquinolones in the treatment of CBP caused by traditional pathogens.Alternative antimicrobial agents tested for the treatment of CBP caused by traditional pathogens are co-trimoxazole, beta-lactams and tetracyclines, but no conclusive evidence can be drawn regarding the role of non-fluoroquinolone antibiotics in the treatment of CBP caused by traditional pathogens.In patients with CBP caused by obligate intracellular pathogens, macrolides showed higher microbiological and clinical cure rates compared to fluoroquinolones.

Abstract
One hundred out-patients, referred to a multidisciplinary pain clinic for the management of chronic pain, were questioned regarding their sleeping habits and were grouped according to whether they reported 'good,' 'fair' or 'poor' sleep. All patients were administered questionnaires to measure illness behaviour, depression and anxiety. Information was also obtained regarding the site, intensity and quality of pain as well as amount of general activity. 'Good' and 'poor' sleepers were found to differ on most measures, particularly depression, pain intensity, activity levels and hypochondriasis. These findings suggest that reported sleep disturbance may provide an index of impairment and act as an indicator of psychological disturbance in chronic pain patients.

Purpose of review: Visceral pain represents a major clinical problem, yet far less is known about its mechanisms compared with somatic pains, for example, from cutaneous and muscular structures.

Recent findings: In this review, we describe the neuroanatomical bases of visceral pain signalling in the peripheral and central nervous system, comparing to somatic pains and also the channels and receptors involved in these events. We include an overview of potential new targets in the context of mechanisms of visceral pain and hypersensitivity.

Summary: This review should inform on the recognition of what occurs in patients with visceral pain, why comorbidities are common and how analgesic treatments work.

Abstract
Background: It remains controversial as to whether delayed gastric emptying in functional dyspepsia is associated with a specific symptom pattern, and it is unknown if gastric emptying in functional dyspepsia is a driver of impaired health related quality of life (HRQOL). We aimed to evaluate the relationship between functional dyspepsia symptoms, gastric emptying, and HRQOL.

Methods: US patients (n=864; mean age 44 years (range 18-82); 74% female) with functional dyspepsia, as defined by Rome II criteria, were enrolled into one of four clinical trials. All patients had a baseline scintigraphic assessment of gastric emptying of an egg substitute meal, and the trials were stratified on this assessment. Delayed gastric emptying was defined as having at least 6.3% residual volume at four hours. A total of 290 (34%) patients had delayed gastric emptying. HRQOL was assessed by the SF 36 and Nepean dyspepsia index (NDI).

Results: Postprandial fullness was independently associated with delayed gastric emptying but the association was weak (odds ratio (OR) 1.98 (95% confidence interval (CI) 1.02, 3.86); p=0.04). No independent association was seen with epigastric pain, early satiety, nausea, or bloating. Mean SF 36 physical composite score (PCS) was 42.3 (95% CI 41.6, 43.0) and the mean SF 36 mental composite score (MCS) was 46.8 (95% CI 46.0, 47.5); both mean scores were significantly lower than age and sex adjusted national norms of 50 (p<.0001). Female sex, increasing age, and higher symptom scores for fullness, epigastric pain, and nausea were each independently associated with decreased PCS scores (all p<0.05). Higher baseline nausea symptom score, lower gastric emptying rates at one hour, and lower body mass index were associated with decreased MCS (all p<0.05). Female sex, epigastric pain, and nausea, but not gastric emptying, were associated with an impaired score on the NDI. However, the magnitude of the significant associations were all small.

Conclusions: In patients with functional dyspepsia selected for a clinical trial programme, gastric emptying did not usefully stratify them symptomatically. Quality of life of patients with functional dyspepsia enrolled in this clinical trial programme was significantly impaired but this was not explained by delayed gastric emptying.

Abstract
Objective: To examine the evolution of pain and the duration of numbness after neural blockade of the pudendal nerve in women with pudendal neuralgia and correlate with clinical and historical data.

Design: Prospective, single arm, open label study.

Setting: University hospital and outpatient clinic.

Subjects: Eighty-two adult female patients were recruited from November 8, 2008 to February 14, 2010. Patients were selected based on the presence of spontaneous or provoked pain in the distribution of the pudendal nerve.

Interventions: Subjects underwent a standardized pudendal nerve block.

Outcome measures: Visual analog pain scores and the presence of numbness were recorded before and for 64 hours after the pudendal nerve block. A complete clinical history and examination were documented.

Results: Sixty-six patients completed the study. About 86.9% had a reduction in one or more pain symptom, while 44.3% found that more than one of their pain symptoms did not return. About 69.7% of patients reported numbness lasting up to 16 hours or longer. Previous gynecological surgery was recorded in 75.8%, previous traumatic obstetric events in 47.0% of cases. Prolonged history of pain correlated with a reduced chance of positive outcome of the pudendal nerve block.

Conclusion: In patients with pudendal neuralgia, the pudendal nerve block has a variable response, but may have a beneficial effect in a subset of women. Surgical and obstetrical trauma are common historical antecedents.

Abstract
Purpose of review: In recent years, sacral neuromodulation (SNM) has been investigated for the treatment of various types of lower urinary tract and bowel dysfunctions. This review discusses recently published data related to the therapeutic applications of SNM in female lower urinary tract, pelvic floor, and bowel disorders.

Recent findings: SNM has been employed initially in the treatment of refractory idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. Since then, several studies, including randomized and controlled trials, have confirmed the therapeutic effects of SNM in these disorders. The applications of SNM are now extended to the treatment of other female pelvic problems, such as fecal incontinence, chronic constipation, interstitial cystitis/painful bladder syndrome, sexual dysfunction, and neurogenic disorders, with similar promising results.

Summary: SNM is approved by the Food and Drug Administration for the treatment of idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. SNM is not yet an approved method for the treatment of other pelvic disorders, but data supporting its benefit are emerging. The major advantage of SNM lies in its potential to treat the bladder, urethral sphincter, anal sphincters, and pelvic floor muscles simultaneously, which might result in better therapeutic effects.

Abstract
Interstitial cystitis (IC) has remained an unresolved problem in clinical urology. The etiology and pathophysiologic mechanisms of IC are still undetermined, and to date the diagnosis is based on the clinical characteristics of the disease and the exclusion of other diseases and pathology that can mimic the symptoms of IC. In clinical practice, much emphasis has been placed on finding a specific etiology and specific pathologic markers for the disease and on identifying specific events that precipitate IC; however, those have not been identified with certainty. In this review, an additional approach is proposed, taking into account the observation that IC shares many features with other chronic nonmalignant visceral pain syndromes. This approach is based on the conceptualization of 3 hypotheses: (1) a spectrum of different insults can lead to chronic visceral pain in patients with IC; (2) different underlying pathogenic pain mechanisms may require different pain treatment strategies for patients diagnosed with IC; and (3) multiple different pathogenic pain mechanisms may coexist in the same patient requiring several different pain treatment strategies (perhaps concomitantly) to successfully treat chronic visceral pain associated with IC. This concept is likely to lead to new insights into the pathophysiologic mechanisms of IC and to novel treatment avenues for patients with IC and-in a broader view-also for patients with other chronic visceral pain syndromes.