Dissociated modulation of conditioned place-preference and mechanical hypersensitivity by a TRPA1 channel antagonist in peripheral neuropathy
| Autor: | Hanna Viisanen, Diana Amorim, Hong Wei, Ari Koivisto, Antti Pertovaara |
|---|---|
| Přispěvatelé: | Universidade do Minho |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Diabetic neuropathy Clinical Biochemistry Transient receptor potential ankyrin 1 channel Toxicology Biochemistry Chembridge-5861528 Mechanical hypersensitivity Behavioral Neuroscience 0302 clinical medicine Diabetic Neuropathies 030202 anesthesiology Conditioning Psychological Adrenergic alpha-2 Receptor Agonists Medicine Conditioned place-preference TRPA1 Cation Channel Ongoing pain Astrophysics::Instrumentation and Methods for Astrophysics Peripheral Nervous System Diseases 3. Good health Clonidine Hyperalgesia Anesthesia Peripheral nerve injury Neuropathic pain medicine.symptom psychological phenomena and processes medicine.drug SNi Astrophysics::Cosmology and Extragalactic Astrophysics Physics::Geophysics 03 medical and health sciences Animals Rats Wistar Biological Psychiatry TRPC Cation Channels Pharmacology Science & Technology business.industry Nerve injury medicine.disease Conditioned place preference Physics::History of Physics Rats Disease Models Animal Peripheral neuropathy Purines Neuralgia Acetanilides business 030217 neurology & neurosurgery |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| Popis: | Uncorrected proof 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 a2-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. One of the authors (A.K.) is an employee of the pharmaceutical company (OrionPharma, Finland) that has supported this study.The study was supported by the Sigrid Juselius Foundation, Helsinki, the Academy of Finland, Helsinki, and OrionPharma, Orion Corporation, Turku, Finland. Diana Amorim was supported by the Portuguese Science Foundation (FCT) grant SFRH/BD/71219/2010. |
| Databáze: | OpenAIRE |
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