Demise of nociceptive Schwann cells causes nerve retraction and pain hyperalgesia
Recent findings indicate that nociceptive nerves are not “free”, but similar to touch and pressure sensitive nerves, terminate in an end-organ in mice. This sensory structure consists of the nociceptive nerves and specialized nociceptive Schwann cells forming a mesh-like organ in subepidermis with pain transduction initiated at both these cellular constituents. The intimate relation of nociceptive nerves with nociceptive Schwann cells in mice raises the question whether defects in nociceptive Schwann cells can by itself contribute to pain hyperalgesia, nerve retraction, and peripheral neuropathy. We therefore examined the existence of nociceptive Schwann cells in human skin and their possible contribution to neuropathy and pain hyperalgesia in mouse models. Similar to mouse, human skin contains SOX10+/S100B+/AQP1+ Schwann cells in the subepidermal border that have extensive processes, which are intimately associated with nociceptive nerves projecting into epidermis. The ablation of nociceptive Schwann cells in mice resulted in nerve retraction and mechanical, cold, and heat hyperalgesia. Conversely, ablating the nociceptive nerves led to a retraction of epidermal Schwann cell processes, changes in nociceptive Schwann cell soma morphology, heat analgesia, and mechanical hyperalgesia. Our results provide evidence for a nociceptive sensory end-organ in the human skin and using animal models highlight the interdependence of the nerve and the nociceptive Schwann cell. ...
This study sheds new light on the functional capability of ECM LAMB1 in modulating pain plasticity and identifies a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified cingulate LAMB1/integrin β1 signaling as a promising therapeutic target for the treatment of neuropathic pain and associated anxiodepression.
CONCLUSIONS: Anorexia, pain and peripheral neuropathy were significantly associated with a decrease in QOL. It is assumed that appropriate pharmaceutical intervention with particular emphasis on these AEs can improve the QOL of pancreatic cancer patients receiving outpatient chemotherapy.PMID:34334136 | DOI:10.1186/s40780-021-00210-1
CONCLUSION: Our results indicate a vital role for IGF-1 signaling in CIPN. Targeting IGF-1 signaling could be a potent therapeutic strategy for treating CIPN in clinical settings.PMID:34333050 | DOI:10.1016/j.brainresbull.2021.07.026
Condition: Diabetic Peripheral Neuropathy Interventions: Dietary Supplement: Vitamin D3; Dietary Supplement: Placebo Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh Recruiting
This study demonstrates a lack of a common neuropathic microglial signature and indicates distinct sex differences in spinal microglia, suggesting they contribute to the sex-specific pain processing following nerve injury.
ConclusionsLocal plantar vibration was effective in improving the symptoms of DPN.
Conditions: Chemotherapy-induced Peripheral Neuropathy; Pain; Solid Tumor Intervention: Drug: Duloxetine Sponsor: Yan Yang, MD, Ph.D Recruiting