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Juarez-Salinas DL, Braz JM, Hamel KA, et al. Pain relief by supraspinal gabapentin requires descending noradrenergic inhibitory controls. Pain Rep. 2018;3(4):e659doi: 10.1097/PR9.0000000000000659.
Juarez-Salinas, D. L., Braz, J. M., Hamel, K. A., & Basbaum, A. I. (2018). Pain relief by supraspinal gabapentin requires descending noradrenergic inhibitory controls. Pain reports, 3(4), e659. https://doi.org/10.1097/PR9.0000000000000659
Juarez-Salinas, Dina L, et al. "Pain relief by supraspinal gabapentin requires descending noradrenergic inhibitory controls." Pain reports vol. 3,4 (2018): e659. doi: https://doi.org/10.1097/PR9.0000000000000659
Juarez-Salinas DL, Braz JM, Hamel KA, Basbaum AI. Pain relief by supraspinal gabapentin requires descending noradrenergic inhibitory controls. Pain Rep. 2018 Jul 17;3(4):e659. doi: 10.1097/PR9.0000000000000659. eCollection 2018. PMID: 30123855; PMCID: PMC6085145.
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Pain Rep. 2018 Jul 17;3(4):e659. doi: 10.1097/PR9.0000000000000659. eCollection 2018.

Pain relief by supraspinal gabapentin requires descending noradrenergic inhibitory controls.

Pain reports

Dina L Juarez-Salinas, Joao M Braz, Katherine A Hamel, Allan I Basbaum

Affiliations

  1. Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.

PMID: 30123855 PMCID: PMC6085145 DOI: 10.1097/PR9.0000000000000659

Abstract

INTRODUCTION: Gabapentin regulates pain processing by direct action on primary afferent nociceptors and dorsal horn nociresponsive neurons. Through an action at supraspinal levels, gabapentin also engages descending noradrenergic inhibitory controls that indirectly regulate spinal cord pain processing. Although direct injection of gabapentin into the anterior cingulate cortex provides pain relief independent of descending inhibitory controls, it remains unclear whether that effect is representative of what occurs when gabapentin interacts at multiple brain loci, eg, after intracerebroventricular (i.c.v.) injection.

METHODS: We administered gabapentin i.c.v. in a mouse model of chemotherapy (paclitaxel)-induced neuropathic pain. To distinguish spinal from supraspinally processed features of the pain experience, we examined mechanical hypersensitivity and assessed relief of pain aversiveness using an analgesia-induced conditioned place preference paradigm.

RESULTS: Paclitaxel-treated mice showed a preference for a 100-μg i.c.v. gabapentin-paired chamber that was accompanied by reduced mechanical allodynia, indicative of concurrent engagement of descending controls. As expected, the same dose in uninjured mice did not induce place preference, demonstrating that gabapentin, unlike morphine, is not inherently rewarding. Furthermore, a lower dose of supraspinal gabapentin (30 μg), which did not reverse mechanical allodynia, did not induce conditioned place preference. Finally, concurrent injections of i.c.v. gabapentin (100 μg) and intrathecal yohimbine, an α2-receptor antagonist, blocked preference for the gabapentin-paired chamber.

CONCLUSION: We conclude that pain relief, namely a reduction of pain aversiveness, induced by supraspinal gabapentin administered by an i.c.v. route is secondary to its activation of descending noradrenergic inhibitory controls that block transmission of the "pain" message from the spinal cord to the brain.

Keywords: Chemotherapy-induced neuropathic pain; Conditioned place preference; Gabapentin; Neuropathic pain; Noradrenergic

Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

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