title: Operant behavioral responses to orofacial cold stimuli in rats with chronic constrictive trigeminal nerve injury: effects of menthol and capsazepine.
abstract: Both spinal and trigeminal somatosensory systems use the TRPM8 channel as a principal transducer for detecting cold stimuli. It is currently unclear whether this cold transducer may play a role in trigeminal neuropathic pain manifesting cold allodynia and hyperalgesia. In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI). Behavioral responses to cold stimuli in orofacial regions were assessed by the newly developed orofacial operant test in the ION-CCI rats. We tested menthol and capsazepine, two compounds that can activate and inhibit TRPM8 respectively, on orofacial operant responses to cold stimuli in ION-CCI rats. Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded. Total contact time was significantly reduced at the cooling temperatures of 17°C and 12°C in ION-CCI group in comparison with sham group, indicating the presence of cold allodynia and hyperalgesia in ION-CCI rats. When menthol was administered to ION-CCI rats, total contact time was further reduced and total contact number increased at the cooling temperatures. In contrast, after administration of capsazepine to ION-CCI rats, total contact time was significantly increased at the cooling temperatures. The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury.
authors.affiliation: Department of Anesthesiology and the Graduate Program in Neuroscience, The University of Cincinnati College of Medicine, Cincinnati, OH 45267-0531, USA.
authors.forename: Xiaozhuo
authors.initials: X
authors.lastname: Zuo
authors.forename: Jennifer X
authors.initials: JX
authors.lastname: Ling
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
authors.forename: Jianguo G
authors.initials: JG
authors.lastname: Gu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003080:Cold Temperature; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D005154:Facial Nerve / Q000378:metabolism / Q000473:pathology; D005157:Facial Pain / Q000378:metabolism; D006930:Hyperalgesia / Q000473:pathology; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D009437:Neuralgia / Q000473:pathology*; D010147:Pain Measurement; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D014276:Trigeminal Nerve / Q000187:drug effects / Q000473:pathology*; D061221:Trigeminal Nerve Injuries / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D008610:Menthol; C071423:capsazepine; D002211:Capsaicin