title: Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice.
abstract: Capsaicin-sensitive, TRPV1 (transient receptor potential vanilloid 1) receptor-expressing primary sensory neurons exert local and systemic efferent effects besides the classical afferent function. The TRPV1 receptor is considered a molecular integrator of various physico-chemical noxious stimuli. In the present study its role was analysed in acute nociceptive tests and chronic neuropathy models by comparison of wild-type (WT) and TRPV1 knockout (KO) mice. The formalin-induced acute nocifensive behaviour, carrageenan-evoked inflammatory mechanical hyperalgesia and partial sciatic nerve lesion-induced neuropathic mechanical hyperalgesia were not different in WT and KO animals. Acute nocifensive behaviour after intraplantar injection of phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), was absent in TRPV1 KO animals showing that PKC activation elicits nociception exclusively through TRPV1 receptor sensitization/activation. Thermal hyperalgesia (drop of noxious heat threshold) and mechanical hyperalgesia induced by a mild heat injury (51 degrees C, 15s) was smaller in KO mice suggesting a pronociceptive role for TRPV1 receptor in burn injury. Chronic mechanical hyperalgesia evoked by streptozotocin-induced diabetic and cisplatin-evoked toxic polyneuropathy occurred earlier and were greater in the TRPV1 KO group. In both polyneuropathy models, at time points when maximal difference in mechanical hyperalgesia between the two groups was measured, plasma somatostatin concentrations determined by radioimmunoassay significantly increased in WT but not in TRPV1 KO mice. It is concluded that sensitization/activation of the TRPV1 receptor plays a pronociceptive role in certain models of acute tissue injury but under chronic polyneuropathic conditions it can initiate antinociceptive counter-regulatory mechanisms possibly mediated by somatostatin released from sensory neurons.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7643, Pécs, Szigeti u. 12, Pecs, Hungary.
authors.forename: Kata
authors.initials: K
authors.lastname: Bölcskei
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.forename: Árpád
authors.initials: Á
authors.lastname: Szabó
authors.forename: Katalin
authors.initials: K
authors.lastname: Sándor
authors.forename: Krisztián
authors.initials: K
authors.lastname: Elekes
authors.forename: József
authors.initials: J
authors.lastname: Németh
authors.forename: Róbert
authors.initials: R
authors.lastname: Almási
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.forename: Gábor
authors.initials: G
authors.lastname: Pethő
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002351:Carrageenan / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects; D004195:Disease Models, Animal; D005557:Formaldehyde / Q000009:adverse effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology; D018345:Mice, Knockout; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000139:chemically induced / Q000145:classification / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D013004:Somatostatin / Q000097:blood; D050916:TRPV Cation Channels / Q000172:deficiency / Q000502:physiology*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D005557:Formaldehyde; D013004:Somatostatin; D002351:Carrageenan; D002945:Cisplatin