title: Dissociated modulation of conditioned place-preference and mechanical hypersensitivity by a TRPA1 channel antagonist in peripheral neuropathy.
abstract: Transient receptor potential ankyrin 1 (TRPA1) channel antagonists have suppressed mechanical hypersensitivity in peripheral neuropathy, while their effect on ongoing neuropathic pain is not yet known. Here, we assessed whether blocking the TRPA1 channel induces place-preference, an index for the relief of ongoing pain, in two experimental rat models of peripheral neuropathy. Diabetic neuropathy was induced by streptozotocin and spared nerve injury (SNI) model of neuropathy by ligation of two sciatic nerve branches. Conditioned place-preference (CPP) paradigm involved pairing of the drug treatment with one of the chambers of a CPP device once or four times, and the time spent in each chamber was recorded after conditioning sessions to reveal place-preference. The mechanical antihypersensitivity effect was assessed by the monofilament test immediately after the conditioning sessions. Intraperitoneally (30mg/kg; diabetic and SNI model) or intrathecally (10μg; diabetic model) administered Chembridge-5861528 (CHEM) was used as a selective TRPA1 channel antagonist. In diabetic and SNI models of neuropathy, CHEM failed to induce CPP at a dose that significantly attenuated mechanical hypersensitivity, independent of the route of drug administration or number of successive conditioning sessions. Intrathecal clonidine (an α2-adrenoceptor agonist; 10μg), in contrast, induced CPP in SNI but not control animals. The results indicate that ongoing pain, as revealed by CPP, is less sensitive to treatment by the TRPA1 channel antagonist than mechanical hypersensitivity in peripheral neuropathy.
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.forename: Hanna
authors.initials: H
authors.lastname: Viisanen
authors.forename: Diana
authors.initials: D
authors.lastname: Amorim
authors.forename: Ari
authors.initials: A
authors.lastname: Koivisto
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage; D003213:Conditioning, Psychological / Q000502:physiology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D058647:Adrenergic alpha-2 Receptor Agonists; D011687:Purines; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D003000:Clonidine