title: Regulation of neuropathic pain behavior by amygdaloid TRPC4/C5 channels.
abstract: Pain per se may increase anxiety and conversely, anxiety may increase pain. Therefore, a positive feedback loop between anxiety and pain possibly contributes to pain and suffering in some pathophysiological pain conditions, such as that induced by peripheral nerve injury. Recent results indicate that transient receptor channels 4 and 5 (TRPC4/C5) in the amygdala have anxiogenic effects in rodents, while their role in chronic pain conditions is not known. Here, we studied whether the amygdaloid TRPC4/C5 that are known to have anxiogenic properties contribute to the maintenance of sensory or affective aspects of pain in an experimental model of peripheral neuropathy. Rats with a spared nerve injury (SNI) model of neuropathy in the left hind limb had a chronic cannula for microinjections of drugs into the right amygdala or the internal capsule (a control site). Sensory pain was assessed by determining mechanical hypersensitivity with calibrated monofilaments and affective pain by determining aversive place-conditioning. Amygdaloid treatment with ML-204, a TRPC4/C5 antagonist, produced a dose-related (5-10 μg) antihypersensitivity effect, without obvious side-effects. Additionally, amygdaloid administration of ML-204 reduced affective-like pain behavior. In the internal capsule, ML-204 had no effect on hypersensitivity or affective-like pain in SNI animals. In healthy controls, amygdaloid administration of ML-204 failed to influence pain behavior induced by mechanical stimulation or noxious heat. The results indicate that the amygdaloid TRPC4/C5 contribute to maintenance of pain hypersensitivity and pain affect in neuropathy.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Boriss
authors.initials: B
authors.lastname: Sagalajev
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: M Anil
authors.initials: MA
authors.lastname: Yüzer
authors.affiliation: Orion Pharma, Orion Corporation, Turku, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Koivisto
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: antti.pertovaara@helsinki.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
mesh_terms: D000339:Affect; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D006930:Hyperalgesia / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014110:Touch
chemical_list: D007211:Indoles; C567966:ML 204; D010880:Piperidines; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; C503500:Trpc5 protein, rat
keywords: Amygdala; Aversive place-conditioning; Descending pain control; Neuropathic pain; Transient receptor potential channels 4 and 5