title: Anesthesia influences neuronal activity and drug effectiveness in neuropathic rats.
abstract: In the study of neuropathic pain, the reduction of spinal neuronal activity by an analgesic drug can inform about site and mechanistic aspects of action. Animal experiments such as in vivo electrophysiological recordings from spinal neurons, however, largely require anesthesia. The impact of the anesthesia on the interpretation of the experimental result has been mostly disregarded. Here we report major differences in basal neuronal activity and the effectiveness of morphine and gabapentin under different anesthetics in the rat neuropathic pain model of chronic constriction injury (CCI). We compared data on basal neuronal activity and drug-induced modulation of spinal wide dynamic range neurons in CCI under isoflurane anesthesia with results under pentobarbital anesthesia. Morphine inhibited spinal neuronal activity in CCI operated rats under both anesthetic conditions. Gabapentin, however, only partially reduced spinal activity when the experiment was performed under pentobarbital anesthesia. A marked inhibitory effect of gabapentin can be revealed by isoflurane anesthesia. It could be expected that drug profiles of clinically active agents are similar across neuropathic pain models. Instead, our results suggest that the choice of the anesthetic influences electrophysiological results to a greater extent than the surgical protocol used to induce nerve injury in an animal model of neuropathic pain.
authors.affiliation: Klinik für Neurologie, Universitätsmedizin Mainz, Mainz, Germany Neuroscience, Physiology and Pharmacology, University College London, London, UK Boehringer Ingelheim Pharma GmbH & Co KG, CNS Research, Biberach, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Hirsch
authors.forename: Anthony
authors.initials: A
authors.lastname: Dickenson
authors.forename: Laura
authors.initials: L
authors.lastname: Corradini
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000588:Amines / Q000494:pharmacology / Q000627:therapeutic use*; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000077206:Gabapentin; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects*; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D012585:Sciatica / Q000188:drug therapy* / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine
keywords: Chronic constriction injury; Gabapentin; Isoflurane; Pentobarbital; Spinal cord