Articles: neuralgia.
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Traumatic peripheral nerve injuries are at high risk of neuropathic pain for which novel effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance. ⋯ The partially crushed nerve was characterized by the sparing of small-diameter myelinated axons and intraepidermal nerve fibers, fewer dorsal root ganglia expressing the injury marker activating transcription factor 3, and lower serum levels of neurofilament light chain. By day 30, axons showed signs of reduced myelin thickness. In summary, the escape of small-diameter axons from Wallerian degeneration is likely a determinant of chronic pain pathophysiology distinct from the general response to complete nerve injury.
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Neuropathic pain impairs quality of life, is widely prevalent, and incurs significant costs. Current pharmacological therapies have poor/no efficacy and significant adverse effects; safe and effective alternatives are needed. Hyperpolarisation-activated cyclic nucleotide-regulated (HCN) channels are causally implicated in some forms of peripherally mediated neuropathic pain. Whilst 2,6-substituted phenols, such as 2,6-di-tert-butylphenol (26DTB-P), selectively inhibit HCN1 gating and are antihyperalgesic, the development of therapeutically tolerable, HCN-selective antihyperalgesics based on their inverse agonist activity requires that such drugs spare the cardiac isoforms and do not cross the blood-brain barrier. ⋯ These findings provide a proof-of-concept demonstration that anchor-tethered drugs are a new chemotype for treatment of disorders involving membrane targets.
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Dorsal root ganglia (DRG) neurons have been well described for their role in driving both acute and chronic pain. Although nerve injury is known to cause transcriptional dysregulation, how this differs across neuronal subtypes and the impact of sex is unclear. Here, we study the deep transcriptional profiles of multiple murine DRG populations in early and late pain states while considering sex. ⋯ We see both stereotyped and unique subtype signatures in injured states after nerve injury at both an early and late timepoint. Although all populations contribute to a general injury signature, subtype enrichment changes can also be seen. Within populations, there is not a strong intersection of sex and injury, but previously unknown sex differences in naïve states-particularly in Aβ-RA + Aδ-low threshold mechanoreceptors-still contribute to differences in injured neurons.
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To evaluate a modification to the classical Hartel technique for the treatment of trigeminal neuralgia. ⋯ Considering the inclusion of the oval foramen in a Cartesian coordinate system with axes X, Y, and Z is useful. Directing the needle to a point located 1 cm from the anterior edge of the TMJ, avoiding the medial aspect of the upper jaw ridge, allows for a safer and faster procedure.
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Review
Cervical Spinal Cord Stimulation for the Treatment of Headache Disorders: A Systematic Review.
Chronic headache remains a major cause of disability and pain worldwide. Although the literature has extensively described pharmacologic options for headache treatment and prophylaxis, there remains a paucity of data on the efficacy of neuromodulation interventions for treatment of headache unresponsive to conventional pharmacologic therapy. The primary aim of this review was to appraise the literature for the efficacy of cervical spinal cord stimulation (cSCS) in treating any intractable chronic headache, including migraine headaches (with or without aura), cluster headache, tension headache, and other types of headaches. ⋯ Our review suggests promising data from observational studies that cSCS may be helpful in decreasing frequency and intensity of chronic intractable headache. Future well-powered, randomized controlled trials are needed.