UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology

Bannister, K; Sikandar, S; Bauer, CS; Dolphin, AC; Porreca, F; Dickenson, AH; (2011) Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology. ANESTHESIOLOGY , 115 (1) 144 - 152. 10.1097/ALN.0b013e31821f6545.

Full text not available from this repository.

Abstract

Background: Opioid-induced hyperalgesia is recognized in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid-induced hyperalgesia.Methods: Male Sprague-Dawley rats (180-200 g) were implanted with osmotic mini-pumps filled with morphine (90 mu g . mu l(-1) . h(-1)) or saline (0.9% w/v). On days 7-10 in isoflurane anesthetized animals, we evaluated the effects of (1) systemic pregabalin on spinal neuronal and visceromotor responses, and (2) spinal ondansetron on dorsal horn neuronal response. Messenger ribonucleic acid concentrations of alpha(2)delta-1, 5HT3A, and mu-opioid receptor in the dorsal root ganglia of all animals were analyzed.Results: In morphine-treated animals, evoked spinal neuronal responses were enhanced to a subset of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%); the visceromotor response to a subset of colorectal distension pressures was attenuated by pregabalin (52.8%; n = 8 for all measures, P < 0.05). Messenger ribonucleic acid concentrations were unchanged.Conclusions: The inhibitory action of pregabalin in opioid-induced hyperalgesia animals is neither neuropathy-dependent nor reliant on up-regulation of the alpha(2)delta-1 subunit of voltage-gated calcium channels-mechanisms proposed as being essential for pregabalin's efficacy in neuropathy. In opioid-induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be up-regulated, creating an environment that is permissive for pregabalin-mediated analgesia without peripheral pathology.

Type: Article
Title: Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology
DOI: 10.1097/ALN.0b013e31821f6545
Keywords: OPIOID-INDUCED HYPERALGESIA, SUSTAINED MORPHINE EXPOSURE, RECEPTOR-EXPRESSING NEURONS, DEPENDENT CALCIUM-CHANNELS, PROTEIN-KINASE-C, NEUROPATHIC PAIN, ANTINOCICEPTIVE TOLERANCE, DESCENDING FACILITATION, RAT MODEL, CENTRAL SENSITIZATION
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1309529
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item