Accepted

There is a lack of good quality evidence regarding the effectiveness of transcutaneous electrical nerve stimulation (TENS) for chronic musculoskeletal pain, including chronic low back pain. High quality randomised controlled trials (RCTs) have been called for to establish effectiveness over and above placebo and some guidance has already been offered regarding the design of such trials. This article expands the discussion regarding the design of future TENS trials. There is qualitative evidence of the complexity of TENS as an intervention which should be considered in future TENS evaluations. This complexity includes multiple benefits reported by patients, depending on their chosen contexts of TENS use. The ideal content and delivery of support for patients to optimise TENS use also lacks consensus. There is no evidence that a TENS education package has been designed to support the complex set of behaviours and choices which experienced users suggest are required to optimise TENS benefits. Finally, clinical and research outcomes have not been contextualised and related to the specific strategies of use. We suggest that research is required to develop consensus about the content and delivery of training in TENS use for patients who live with pain, informed by the experience of patients, clinicians, and researchers. Once a consensus about the content of TENS training has been reached, there is then a need to develop a TENS training course (TTC) based on this content. An effective and acceptable TTC is needed to develop the knowledge and skills required to optimise TENS use, supporting patients to build confidence in using TENS in everyday life situations with the aim of reducing the impact of chronic pain on function and quality of life. Further research is required to extend the evidence base regarding appropriate, contextualised TENS patient-reported outcomes.

Migraine is indeed a neurovascular disorder for which several genes have been identified in this era of Genome-Wide Association Studies (GWAS) and neuroimaging studies have already revealed structural changes and different mechanisms that cause migraine, but the exact cause of this debilitating and disabling neurovascular disorder remained unclear. Low neuronal hyperexcitability ("the migrainous brain") is set and hindered by genetic and environmental factors, respectively. Migraine is also found to be associated with different diseases (co-morbidity). There is still a subject of contention: is migraine a disease of evolution or disease of pathology? This research review seeks to provide a brief overview on the genetics of disorders, structural abnormalities in the brain, CSD-like symptoms, and faulty Trigeminovascular System activation for migraine pain phenotype. This review briefly covered here to provide some ideas that may also be utilized in migraine research and to serve as motivation for future research.

Chronic neck and shoulder pain (CNSP) is a common neurological disorder, which females are more likely to suffer from. The periaqueductal gray (PAG) plays a key role in the descending modulation of pain. This study aimed to investigate altered PAG-based functional connectivity (FC) in female patients with CNSP related to healthy controls (HCs) and the effect of acupuncture for female patients with CNSP using PAG-based FC biomarkers.

In their Matters Arising article, McMullan et al. (2022) offer alternative explanations for the phenotypes we observed upon stimulation and ablation of TrkC-positive neurons in mice. Their interpretations are focused on two aspects: first, whether the vasoconstriction we observed upon activation of TrkC neurons is really mediated by TrkC/TH-positive neurons, or whether it might stem from stimulation of somatic nociceptors that also express TrkC; and second, whether the lethality observed after ablation of TrkC neurons might be a result of ablation of vagal afferents and not TrkC/TH neurons located in the spinal ganglia. Central to both of these concerns is the expression and recombination efficiency of the TrkC transgene in these other cell types. This Matters Arising Response paper addresses the McMullan et al. (2022) Matters Arising paper, published concurrently in Cell Reports.

This article was not intended to be a complete review of the electromyography of pathological muscle states, but it was written to illustrate how the "Coletti Method of EMG ChemoDenervation" (CMECD®) protocol for the treatment of chronic pain resulting from chronic muscle spasm was developed and established. That process led to an unexpected understanding of the underlying pathophysiology of chronic muscle spasm, which represents a paradigm shift in our understanding and ultimately in our treatment of muscle spasm-induced chronic pain. Other investigators had brought to light the presence of spontaneous electrical activity (SEA) in states of muscle spasm. Those findings were all but ignored by standard EMG/Nerve conduction studies in clinical practice. Starting with a simple EMG device I experimented with various medications to treat patients with chronic pain associated with chronic muscle spasm. Suppression of SEA with long-acting medications resolved both the chronic spasm and chronic pain. A successful protocol using phenoxybenzamine was established and clinical outcomes were followed. More than 200 patients were successfully treated during last 12 years. Correlating known exercise muscle physiology with the development of the pathological state of chronic muscle spasm as seen by electromyography led to the postulation of the ischemic model of chronic muscle spasm. Light microscopy pathophysiologic supportive findings are presented and discussed. Predictions from this model to various aspects of treatment were supportive. Implications regarding treatment by the CMECD procedure, as well as other standard therapies, are discussed. Application of the ischemic model to other pain conditions was explored with implications of therapeutic modification. Recommendations for changes in rehabilitation therapy are discussed.

Noxious stimuli like cold, heat, pH change, tissue damage, and inflammation depolarize a membrane of peripheral endings of specialized nociceptive neurons which eventually results in the generation of an action potential. The electrical signal is carried along a long axon of nociceptive neurons from peripheral organs to soma located in dorsal root ganglions and further to the dorsal horn of the spinal cord where it is transmitted through a chemical synapse and is carried through the spinal thalamic tract into the brain. Two subtypes of voltage-activated calcium play a major role in signal transmission: a low voltage-activated Ca3.2 channel and a high voltage-activated Ca2.2 channel. The Ca3.2 channel contributes mainly to the signal conductance along nociceptive neurons while the principal role of the Ca2.2 channel is in the synaptic transmission at the dorsal horn. Both channels contribute to the signal initiation at peripheral nerve endings. This review summarizes current knowledge about the expression and distribution of these channels in a nociceptive pathway, the regulation of their expression and gating during pain pathology, and their suitability as targets for pharmacological therapy.

Extremely low-frequency electromagnetic field (ELF-MF) therapy is a promising treatment for chronic pain, given its ability to interact with body homeostasis using water-mediated transmission mechanisms typical of quantum medicine. The present study aims to assess the effects of ELF-MF therapy on chronic pain in 49 patients suffering from various musculoskeletal disorders. The therapy was applied through a Quec Phisis setup generating the electromagnetic field as the ion cyclotronic resonance. Patients underwent eight therapy sessions of 45 min each performed every other day. The bioimpedance assessment was based on the comparison of the height-adjusted body resistance (R/h) and reactance (Xc/h) measured during the first and last sessions of eight-session treatment. Pain perception was quantified using the standard visual-analog scale. We found significant increases in both R/h and Xc/h parameters of body bioimpedance after electromagnetic therapy corresponding with reductions in pain perception. We conclude that the ELF-MF therapy can restore the body's state of health and thus seems a valid therapeutic approach for the treatment of musculoskeletal-derived pain.