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Purpose of Review Our goal is to examine the processes—both central and peripheral—that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent evidence for mechanisms contributing to its maintenance. While many pNP conditions are initiated by damage to the peripheral nervous system (PNS), their persistence appears to rely on maladaptive processes within the central nervous system (CNS). The potential existence of an autonomous pain-generating mechanism in the CNS creates significant implications for the development of new neuropathic pain treatments; thus, work towards its resolution is crucial. Here, we seek to identify evidence for PNS and CNS independently generating neuropathic pain signals. Recent Findings Recent preclinical studies in pNP support and provide key details concerning the role of multiple mechanisms leading to fiber hyperexcitability and sustained electrical discharge to the CNS. In studies regarding central mechanisms, new preclinical evidence includes the mapping of novel inhibitory circuitry and identification of the molecular basis of microglia-neuron crosstalk. Recent clinical evidence demonstrates the essential role of peripheral mechanisms, mostly via studies that block the initially damaged peripheral circuitry. Clinical central mechanism studies use imaging to identify potentially self-sustaining infra-slow CNS oscillatory activity that may be unique to pNP patients. Summary While new preclinical evidence supports and expands upon the key role of central mechanisms in neuropathic pain, clinical evidence for an autonomous central mechanism remains relatively limited. Recent findings from both preclinical and clinical studies recapitulate the critical contribution of peripheral input to maintenance of neuropathic pain. Further clinical investigations on the possibility of standalone central contributions to pNP may be assisted by a reconsideration of the agreed terms or criteria for diagnosing the presence of central sensitization in humans.

Purpose of Review This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain. Recent Findings Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Summary Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians.

Purpose of Review Topical therapeutic approaches in localized neuropathic pain (LNP) syndromes are increasingly used by both specialists and general practitioners, with a potentially promising effect on pain reduction. In this narrative review, we describe the available compounds for topical use in LNP syndromes and address their potential efficacy according to the literature. Recent Findings Local anaesthetics (e.g., lidocaine, bupivacaine and mepivacaine), as well as general anaesthetic agents (e.g., ketamine), muscle relaxants (e.g., baclofen), capsaicin, anti-inflammatory drugs (e.g., diclofenac), salicylates, antidepressants (e.g., amitriptyline and doxepin), α2 adrenergic agents (e.g., clonidine), or even a combination of them have been tested in various applications for the treatment of LNP. Few of them have reached a sufficient level of evidence to support systematic use as treatment options. Summary Relatively few systemic side effects or drug–drug interactions and satisfactory efficacy seem to be the benefits of topical treatments. More well-organized and tailored studies are necessary for the further conceptualization of topical treatments for LNP.

Pain is an important innate defense mechanism that can dramatically alter a person’s quality of life. Understanding the microbiological and physiological effects of pain may be important in the pursuit of novel pain interventions. The three descriptors of pain recognized by the International Association for the Study of Pain are nociceptive, neuropathic, and nociplastic pain. Our review examined the current understanding of all three pain types, focusing on the key molecules involved in the manifestation of each type as well as physiological effects. Additionally, we compared the differences in painful and painless neuropathies and discussed the neuroimmune interaction involved in the manifestation of pain.

Purpose of Review Researchers suggests that patients with COVID-19 develop neuropathic pain within weeks or months following infection and that patients with neuropathic pain and COVID-19 sometimes present with deterioration of neurologic complications and pain exacerbation. The objective of this systematic review is to discuss the case-reports having neuropathic pain during and after COVID-19 infection. Recent Findings Case reports that has described about patients getting neuropathy or neuropathic pain around the disease either immediately or late post COVID were included. The data was extracted and qualitatively synthesised. Literature was searched and 939 articles were found. 12 articles were screened as per the eligibility criteria and finally, 6 case reports on neuropathic pain in Covid-19 were selected from the database and manual search and finalised for analysis. 2 cases of herpes zoster and post herpetic neuralgia, 2 cases of intense burning pain, 1 case of trigeminal neuralgia and 1 of brachial plexopathy included for the review. Summary Covid 19 viral neurogenic invasion is something very newly discovered topic of discussion in the field of research. With the passage of time, more cases will emerge and more data will be available for research. The review is registered in Prospero with no. CRD42021257060.

The development of chronic pain is a complex mechanism that is still not fully understood. Multiple somatic and visceral afferent pain signals, when experienced over time, cause a strengthening of certain neural circuitry through peripheral and central sensitization, resulting in the physical and emotional perceptual chronic pain experience. The mind-altering qualities of psychedelics have been attributed, through serotonin 2A (5-HT2A) receptor agonism, to ‘reset’ areas of functional connectivity (FC) in the brain that play prominent roles in many central neuropathic states. Psychedelic substances have a generally favorable safety profile, especially when compared with opioid analgesics. Clinical evidence to date for their use for chronic pain is limited; however, several studies and reports over the past 50 years have shown potential analgesic benefit in cancer pain, phantom limb pain and cluster headache. While the mechanisms by which the classic psychedelics may provide analgesia are not clear, several possibilities exist given the similarity between 5-HT2A activation pathways of psychedelics and the nociceptive modulation pathways in humans. Additionally, the alterations in FC seen with psychedelic use suggest a way that these agents could help reverse the changes in neural connections seen in chronic pain states. Given the current state of the opioid epidemic and limited efficacy of non-opioid analgesics, it is time to consider further research on psychedelics as analgesics in order to improve the lives of patients with chronic pain conditions.

Purpose of Review This review presents the most current information about the epidemiology of complex regional pain syndrome (CRPS), classification and diagnostic criteria, childhood CRPS, subtypes, pathophysiology, conventional and less conventional treatments, and preventive strategies. Recent Findings CRPS is a painful disorder with multifactorial pathophysiology. The data describe sensitization of the central and peripheral nervous systems, inflammation, possible genetic factors, sympatho-afferent coupling, autoimmunity, and mental health factors as contributors to the syndrome. In addition to conventional subtypes (type I and type II), cluster analyses have uncovered other proposed subtypes. Prevalence of CRPS is approximately 1.2%, female gender is consistently associated with a higher risk of development, and substantial physical, emotional, and financial costs can result from the syndrome. Children with CRPS seem to benefit from multifaceted physical therapy leading to a high percentage of symptom-free patients. The best available evidence along with standard clinical practice supports pharmacological agents, physical and occupational therapy, sympathetic blocks for engaging physical restoration, steroids for acute CRPS, neuromodulation, ketamine, and intrathecal baclofen as therapeutic approaches. There are many emerging treatments that can be considered as a part of individualized, patient-centered care. Vitamin C may be preventive. Summary CRPS can lead to progressively painful sensory and vascular changes, edema, limb weakness, and trophic disturbances, all of which substantially erode healthy living. Despite some progress in research, more comprehensive basic science investigation is needed to clarify the molecular mechanisms of the disease so that targeted treatments can be developed for better outcomes. Incorporating a variety of standard therapies with different modes of action may offer the most effective analgesia. Introducing less conventional approaches may also be helpful when traditional treatments fail to provide sufficient improvement.

Purpose of Review Many cultures throughout history have used cannabis to treat a variety of painful ailments. Neuropathic pain is a complicated condition that is challenging to treat with our current medications. Recent scientific discovery has elucidated the intricate role of the endocannabinoid system in the pathophysiology of neuropathic pain. As societal perceptions change, and legislation on medical cannabis relaxes, there is growing interest in the use of medical cannabis for neuropathic pain. Recent Findings We examined current basic scientific research and data from recent randomized controlled trials (RCTs) evaluating medical cannabis for the treatment of neuropathic pain. These studies involved patients with diverse etiologies of neuropathic pain and included medical cannabis with different THC concentrations and routes of administration. Multiple RCTs demonstrated efficacy of medical cannabis for treating neuropathic pain, with number needed to treat (NNT) values similar to current pharmacotherapies. Summary Although limited by small sample sizes and short duration of study, the evidence appears to support the safety and efficacy of short-term, low-dose cannabis vaporization and oral mucosal delivery for the treatment of neuropathic pain. The results suggest medical cannabis may be as tolerable and effective as current neuropathic agents; however, more studies are needed to determine the long-term effects of medical cannabis use. Furthermore, continued research to optimize dosing, cannabinoid ratios, and alternate routes of administration may help to refine the therapeutic role of medical cannabis for neuropathic pain.

Purpose of Review Transcutaneous electrical nerve stimulation (TENS) is widely used as a non-pharmacological approach for pain relief in a variety of clinical conditions. This manuscript aimed to review the basic mechanisms and clinical applications regarding the use of TENS for alleviating the peripheral (PNP) and central neuropathic pain (CNP). Recent Findings Basic studies on animal models showed that TENS could alleviate pain by modulating neurotransmitters and receptors in the stimulation site and its upper levels, including the spinal cord, brainstem, and brain. Besides, many clinical studies have investigated the efficacy of TENS in patients with CNP (caused by spinal cord injury, stroke, or multiple sclerosis) and PNP (induced by diabetes, cancer, or herpes zoster). Most clinical trials have demonstrated the efficacy of TENS in attenuating neuropathic pain and suggested that appropriate stimulation parameters (e.g., stimulation frequency and intensity) were critical to improving the analgesic effects of TENS. However, there are some conflicting findings related to the efficacy of TENS in relieving neuropathic pain. Summary With optimized stimulation parameters, TENS would be effective in attenuating neuropathic pain. To obtain sufficient evidence to support the use of TENS in the clinic, researchers recommended performing multicenter clinical trials with optimized TENS protocols for the treatment of various CNP and PNP.

Purpose of Review This narrative review aims to summarize advances in the field of small fiber neuropathy made over the last decade, with emphasis on novel research highlighting the distinctive features of SFN. Recent Findings While the management of SFNs is ideally aimed at treating the underlying cause, most patients will require pain control via multiple, concurrent therapies. Herein, we highlight the most up-to-date information for diagnosis, medication management, interventional management, and novel therapies on the horizon. Summary Despite the prevalence of small fiber neuropathies, there is no clear consensus on guidelines specific for the treatment of SFN. Despite the lack of specific guidelines for SFN treatment, the most recent general neuropathic pain guidelines are based on Cochrane studies and randomized controlled trials (RCTs) which have individually examined therapies used for the more commonly studied SFNs, such as painful diabetic neuropathy and HIV neuropathy. The recommendations from current guidelines are based on variables such as number needed to treat (NNT), safety, ease of use, and effect on quality of life.