This article examines the biological, genetic, and environmental aspects of fibromyalgia that may have an impact on its pathogenesis. Symptoms of fibromyalgia may be related to aberrations in the endogenous inhibition of pain as well as changes in the central processing of sensory input. Genetic research has revealed familial aggregation of fibromyalgia and other related disorders like major depressive disorder. Dysfunctional pain processing may also be influenced by exposure to physical or psychological stressors, abnormal biologic reactions in the autonomic nervous system, and neuroendocrine responses. With more research the pathophysiology of fibromyalgia will be better understood, leading to more logical and focused treatment options for fibromyalgia patients.

The use of stimulation of peripheral nerves to test or treat various medical disorders has been prevalent for a long time. Over the last few years, there has been growing evidence for the use of peripheral nerve stimulation (PNS) for treating a myriad of chronic pain conditions such as limb mononeuropathies, nerve entrapments, peripheral nerve injuries, phantom limb pain, complex regional pain syndrome, back pain, and even fibromyalgia. The ease of placement of a minimally invasive electrode via percutaneous approach in the close vicinity of the nerve and the ability to target various nerves have led to its widespread use and compliance. While most of the mechanism behind its role in neuromodulation is largely unknown, the gate control theory proposed by Melzack and Wall in the 1960s has been the mainstay for understanding its mechanism of action. In this review article, the authors performed a literature review to discuss the mechanism of action of PNS and discuss its safety and usefulness in treating chronic pain. The authors also discuss current PNS devices available in the market today.

Background Cryotherapy has been used to reduce chronic pain for many years due in part to its ease of use, affordability, and simplicity. It can be applied either locally (e.g., ice packs) or non-locally (e.g., partial and whole-body cryotherapy) depending on the location of the pain. Objectives To determine the overall effectiveness of cryotherapy at reducing chronic pain by characterizing the currently available evidence supporting the use and effects of cryotherapy on chronic pain associated with chronic diseases. Study Design A narrative review of original research studies assessing the efficacy of cryotherapy in alleviating chronic pain. Methods A PubMed database search was performed to find human studies between the years 2000 and 2020 that included the application of cryotherapy in patients with chronic pain associated with chronic diseases. A review of the relevant references was also performed to gather more articles. Data was extracted, summarized into tables, and qualitatively analyzed. Results Twenty-five studies (22 randomized controlled trials, one prospective analysis, 1 one-group pretest/posttest study, and one case–control study) were included after the literature search. Both local and non-local cryotherapy applications show promise in reducing chronic pain associated with various chronic diseases including those of rheumatic and degenerative origin. Cryotherapy appears to be a safe therapy in carefully selected patients, with only minimal adverse effects reported in the literature. Limitations Meta-analysis was not possible given the many differences between studies. Cross-study data homogenization and comparison between studies proved fairly difficult due to the lack of standardized studies, various uses and practice types of cryotherapy, and lack of control groups in some studies. Conclusions Local and non-local cryotherapy can be low-risk and easy treatment options to add in the management of chronic pain in carefully selected patients. However, long-term effects, a standardized approach, and careful study of other chronic pain syndromes should be considered in future research to further support the use of cryotherapy in the management of chronic pain.

Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review, we aim to contribute to the evolving understanding and management of fibromyalgia, offering insights into the diverse tools available to improve the lives of those affected by this challenging condition. Management begins with educating patients to ultimately relieve them of unnecessary testing and provide reassurance. Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, exercise, and psychotherapy, alongside pharmacologic management—namely duloxetine, milnacipran, pregabalin, and amitriptyline—which have consistent benefits for a range of symptoms across the spectrum of fibromyalgia. Notably, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are generally not recommended due to limited efficacy and associated risks. Lastly, a variety of other medications have shown promise, including NMDA-receptor antagonists, naltrexone, and cannabinoids; however, they should be used with caution due to a small amount of evidence and potential for adverse effects.

Background: Hyperexcitability of nociceptive afferent fibers is an underlying mechanism of neuropathic pain and ion channels involved in neuronal excitability are potentially therapeutic targets. KCNQ channels, a subfamily of voltage-gated K⁺ channels mediating M-currents, play a key role in neuronal excitability. It is unknown whether KCNQ channels are involved in the excitability of nociceptive cold-sensing trigeminal afferent fibers and if so, whether they are therapeutic targets for orofacial cold hyperalgesia, an intractable trigeminal neuropathic pain. Methods: Patch-clamp recording technique was used to study M-currents and neuronal excitability of cold-sensing trigeminal ganglion neurons. Orofacial operant behavioral assessment was performed in animals with trigeminal neuropathic pain induced by oxaliplatin or by infraorbital nerve chronic constrictive injury. Results: We showed that KCNQ channels were expressed on and mediated M-currents in rat nociceptive cold-sensing trigeminal ganglion (TG) neurons. The channels were involved in setting both resting membrane potentials and rheobase for firing action potentials in these cold-sensing TG neurons. Inhibition of KCNQ channels by linopirdine significantly decreased resting membrane potentials and the rheobase of these TG neurons. Linopirdine directly induced orofacial cold hyperalgesia when the KCNQ inhibitor was subcutaneously injected into rat orofacial regions. On the other hand, retigabine, a KCNQ channel potentiator, suppressed the excitability of nociceptive cold-sensing TG neurons. We further determined whether KCNQ channel could be a therapeutic target for orofacial cold hyperalgesia. Orofacial cold hyperalgesia was induced in rats either by the administration of oxaliplatin or by infraorbital nerve chronic constrictive injury. Using the orofacial operant test, we showed that retigabine dose-dependently alleviated orofacial cold hyperalgesia in both animal models. Conclusion: Taken together, these findings indicate that KCNQ channel plays a significant role in controlling cold sensitivity and is a therapeutic target for alleviating trigeminal neuropathic pain that manifests orofacial cold hyperalgesia.

Electrical stimulation of peripheral nerves has been utilized for a variety of indications for over five decades