Pain medicine basics: Overview

Neuromodulation: Technology at the Neural Interface is the preeminent journal in the area of neuromodulation, providing our readership with the state of the art clinical, translational and basic science research in our field and representing the needs of the broad neuromodulation community. For clinicians, engineers, scientists and members of the biotechnology industry alike, Neuromodulation provides timely and rigorously peer reviewed articles on the technology, science and clinical application of devices that interface with the nervous system to treat disease and improve function. Neuromodulation covers an ever expanding field including pain, headache, movement disorders, spasticity, paralysis, psychiatric disorders, epilepsy, sensory deprivation, gastric dysfunction, obesity and incontinence.

Regional Anesthesia & Pain Medicine, the official publication of the American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine), is a monthly journal that publishes peer-reviewed scientific and clinical studies to advance the understanding and clinical application of regional techniques for surgical anesthesia and postoperative analgesia. Coverage includes intraoperative regional techniques, perioperative pain, chronic pain, obstetric anesthesia, paediatric anesthesia, outcome studies, and complications.

Abstract
Objectives: This study aimed to compare the analgesic effects of continuous femoral nerve block (FNB), femoral triangle block (FTB), and adductor canal block (ACB) following total knee arthroplasty (TKA). The goal was to identify the most effective nerve block technique among these three.

Methods: Patients undergoing TKA were randomly assigned to one of three groups: FNB, FTB, or ACB. Nerve blocks were administered preoperatively, with catheters placed for patient-controlled nerve analgesia (PCNA). The primary endpoint was the Numeric Rating Scale (NRS) score at movement at 24 hours post-surgery. Secondary endpoints included NRS scores at rest and movement, quadriceps strength, Timed Up and Go (TUG) test performance, range of motion (ROM), effective PCNA utilization, and opioid consumption at various post-surgery time points.

Results: Of the 94 valid datasets analyzed (FNB: 31, FTB: 31, ACB: 32), significant differences were observed in the primary endpoint (H=7.003, P=0.03). Post-hoc analysis with Bonferroni correction showed that the FNB group had a significantly lower median pain score (3 [2-4]) compared to the ACB group (4 [3-5], Bonferroni-adjusted P=0.03). Regarding secondary endpoints, both the FNB and FTB groups had lower NRS scores than the ACB group at various time points after surgery. Quadriceps strength and TUG completion were better in the FTB and ACB groups. There were no statistically significant differences among the groups for the other endpoints.

Discussion: Continuous FTB provides postoperative analgesia comparable to FNB, but with the advantage of significantly less impact on quadriceps muscle strength, a benefit not seen with FNB. Both FTB and ACB are effective in preserving quadriceps strength postoperatively.

Abstract
Migraine is a complex and highly incapacitating neurological disorder that affects around 15% of the general population with greater incidence in women, often at the most productive age of life. Migraine physiopathology is still not fully understood, but it involves multiple mediators and events in the trigeminovascular system and the central nervous system. The identification of calcitonin gene-related peptide as a key mediator in migraine physiopathology has led to the development of effective and highly selective antimigraine therapies. However, this treatment is neither accessible nor effective for all migraine sufferers. Thus, a better understanding of migraine mechanisms and the identification of potential targets are still clearly warranted. Voltage-gated calcium channels (VGCCs) are widely distributed in the trigeminovascular system, and there is accumulating evidence of their contribution to the mechanisms associated with headache pain. Several drugs used in migraine abortive or prophylactic treatment target VGCCs, which probably contributes to their analgesic effect. This review aims to summarize the current evidence of VGGC contribution to migraine physiopathology and to discuss how current pharmacological options for migraine treatment interfere with VGGC function. PERSPECTIVE: Calcitonin gene-related peptide (CGRP) represents a major migraine mediator, but few studies have investigated the relationship between CGRP and VGCCs. CGRP release is calcium channel-dependent and VGGCs are key players in familial migraine. Further studies are needed to determine whether VGCCs are suitable molecular targets for treating migraine.

Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of β-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids.