Spinal glycinergic currents are reduced in a rat model of neuropathic pain following partial nerve ligation but not chronic constriction injury

• Published in: Journal of neurophysiology 2023-02, Vol.129 (2), p.333-341
• Main Authors: Natale, Claudia A, Christie, Macdonald J, Aubrey, Karin R
• Format: Article
• Language: English
• Subjects: Animals; Constriction; Neuralgia; Neurons; Rats; Rats, Sprague-Dawley; Spinal Cord; Substantia Gelatinosa
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00451.2022

Animal models have consistently indicated that central sensitization and the development of chronic neuropathic pain are linked to changes to inhibitory signaling in the dorsal horn of the spinal cord. However, replication of data investigating the cellular mechanisms that underlie these changes remains a challenge and there is still a lack of understanding about what aspects of spinal inhibitory transmission most strongly contribute to the disease. Here, we compared the effect of two different sciatic nerve injuries commonly used to generate rodent models of neuropathic pain on spinal glycinergic signaling. Using whole cell patch-clamp electrophysiology in spinal slices, we recorded from neurons in the lamina II of the dorsal horn and evoked inhibitory postsynaptic currents with a stimulator in lamina III, where glycinergic cell bodies are concentrated. We found that glycine inputs onto radial neurons were reduced following partial nerve ligation (PNL) of the sciatic nerve, consistent with a previous report. However, this finding was not replicated in animals that underwent chronic constriction injury (CCI) to the same nerve region. To limit the between-experiment variability, we kept the rat species, sex, and age consistent and had a single investigator carry out the surgeries. These data show that PNL and CCI cause divergent spinal signaling outcomes in the cord and add to the body of evidence suggesting that treatments for neuropathic pain should be triaged according to nerve injury or cellular dysfunction rather than the symptoms of the disease. Neuropathic pain models are used in preclinical research to investigate the mechanisms underlying allodynia, a common symptom of neuropathic pain, and to test, develop, and validate therapies for persistent pain. We demonstrate that a glycinergic dysfunction is consistently associated with partial nerve ligation but not the chronic constriction injury model. This suggests that the cellular effects produced by each injury are distinct and that data from different neuropathic pain models should be considered separately.