title: Possible involvement of TRPV1 and TRPV4 in nociceptive stimulation- induced nocifensive behavior and neuroendocrine response in mice.
abstract: Members of the transient receptor potential (TRP) family of ion channels play important roles in inflammation and pain. Here, we showed that both TRPV1 and TRPV4 might contribute to biphasic nocifensive behavior and neuroendocrine response following a formalin test. We subcutaneously injected saline, formalin, or the TRPV4 agonist, 4α-phorbol 12,13-didecanoate (4α-PDD) into one hindpaw of wild-type (WT), TRPV1-deficient (Trpv1(-/-)), and TRPV4-deficient (Trpv4(-/-)) mice to investigate nocifensive behaviors (phase I [0-10 min] and phase II [10-60 min]) and Fos expression in the dorsal horn of the spinal cord and other brain regions related to pain, in the paraventricular nucleus (PVN), paraventricular nucleus of the thalamus, the medial habenular nucleus, the medial nucleus of the amygdala and capsular part of the central amygdala. Subcutaneous (s.c.) injection of formalin caused less nocifensive behavior in Trpv1(-/-) and Trpv4(-/-) mice than in WT mice during phase I. In phase II, however, formalin induced less nocifensive behavior only in the Trpv1(-/-) mice, but not in the Trpv4(-/-) mice, relative to WT mice. The number of Fos-like immunoreactive (LI) neurons in laminae I-II of the dorsal horn increased in all types of mice 90 min after s.c. injection of formalin; however, there was no difference in the other regions between saline- and formalin-treated mice. Furthermore, s.c. injection of 4α-PDD did not induce nociceptive behavior nor influence the number of Fos-LI neurons in the all above mentioned regions in any of the mice. These results suggest that TRPV4-mediated nociceptive information from the peripheral tissue excluding the spinal pathway might be involved the formalin behavioral response during phase I. Only TRPV1 might regulate the formalin behavioral response in peripheral neuron.
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Orthopaedics, Youmeikai Obase Hospital, Kanda, Fukuoka 800-0344, Japan.
authors: Toru
authors: T
authors: Ishikura
authors: Department of Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Hitoshi
authors: H
authors: Suzuki
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Kanako
authors: K
authors: Shoguchi
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Yuki
authors: Y
authors: Koreeda
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Takafumi
authors: T
authors: Aritomi
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Takanori
authors: T
authors: Matsuura
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Mitsuhiro
authors: M
authors: Yoshimura
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Jun-ichi
authors: J
authors: Ohkubo
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Takashi
authors: T
authors: Maruyama
authors: Department of Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Makoto
authors: M
authors: Kawasaki
authors: Department of Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Hideo
authors: H
authors: Ohnishi
authors: Department of Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors: Akinori
authors: A
authors: Sakai
authors: Department of Pharmacology, Jichi Medical University, Minamikawachi, Tochigi 329-0498, Japan.
authors: Atsuko
authors: A
authors: Mizuno
authors: Edogawabashi Suzuki Clinic, Shinjyukuku, Tokyo 162-0801, Japan.
authors: Makoto
authors: M
authors: Suzuki
authors: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan. Electronic address: yoichi@med.uoeh-u.ac.jp.
authors: Yoichi
authors: Y
authors: Ueta
mesh_terms: D000818:Animals; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009490:Neurosecretory Systems / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D010703:Phorbol Esters; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000172:deficiency / Q000378:metabolism*
chemical_list: D010703:Phorbol Esters; D016760:Proto-Oncogene Proteins c-fos; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C486576:Trpv4 protein, mouse; C008876:phorbol-12,13-didecanoate
keywords: Formalin test; Neuroendocrine response; Nocifensive behavior; TRPV1; TRPV4