Neuropathic Pain: Mechanisms, Sex Differences, and Potential Therapies for a Global Problem

Abstract

The study of chronic pain continues to generate ever-increasing numbers of publications, but safe and efficacious treatments for chronic pain remain elusive. Recognition of sex-specific mechanisms underlying chronic pain has resulted in a surge of studies that include both sexes. A predominant focus has been on identifying sex differences, yet many newly identified cellular mechanisms and alterations in gene expression are conserved between the sexes. Here we review sex differences and similarities in cellular and molecular signals that drive the generation and resolution of neuropathic pain. The mix of differences and similarities reflects degeneracy in peripheral and central signaling processes by which neurons, immune cells, and glia codependently drive pain hypersensitivity. Recent findings identifying critical signaling nodes foreshadow the development of rationally designed, broadly applicable analgesic strategies. However, the paucity of effective, safe pain treatments compels targeted therapies as well to increase therapeutic options that help reduce the global burden of suffering.

Conserved transcriptional programming across sex and species after peripheral nerve injury predicts treatments for neuropathic pain

“…Syk is known to be expressed strongly in immune cells particularly macrophages, microglia, dendritic cells and B lymphocytes (Mócsai et al, 2010). The reversal of mechanical hypersensitivity by R406 in females as well as males may seem to suggest that the cell type affected by this drug is not microglia, as interventions that suppress microglia differentially reverse pain hypersensitivity in males but not in females (Ghazisaeidi et al, 2023). This would be the case if one were to consider that R406 and P505‐15 might only act to suppress pain‐promoting mechanisms in microglia.…”

“…The focus of the present paper on sex-conserved and speciesconserved genes may seem contrary to a goal of considering sex as a biological variable in chronic pain (Ghazisaeidi et al, 2023). This focus was revealed by the results of our experimental and analytical design, and was only possible by examining both sexes and both species of rodents.…”

Tapentadol: A Review of Experimental Pharmacology Studies, Clinical Trials, and Recent Findings

“…There are many potential causes of neuropathic pain, including peripheral neuropathies, spinal cord injuries, and brain lesions). 48 The signs and symptoms of neuropathic pain are often characterized by sensory losses (eg, hypoesthesia and hypoalgesia) and/or sensory gains (eg, tactile and mechanical allodynia). 48 Furthermore, the intensity of these symptoms can vary from person to person, ranging from mild to severe.…”

“…There are many potential causes of neuropathic pain, including peripheral neuropathies, spinal cord injuries, and brain lesions). 48 The signs and symptoms of neuropathic pain are often characterized by sensory losses (eg, hypoesthesia and hypoalgesia) The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule.…”

“…and/or sensory gains (eg, tactile and mechanical allodynia). 48 Furthermore, the intensity of these symptoms can vary from person to person, ranging from mild to severe. Steigerwald, Ilona et al evaluated patients with severe chronic low back pain accompanied by neuropathic pain using tapentadol prolonged release (PR).…”