title: Transient receptor potential ankyrin 1 in spinal cord dorsal horn is involved in neuropathic pain in nerve root constriction rats.
abstract: BACKGROUND
  Lumbar radicular pain is categorized as a type of neuropathic pain, but its pathophysiological mechanisms are not fully understood. The substantia gelatinosa (SG) in the spinal cord dorsal horn receives primary afferent inputs and is considered to be a therapeutic target for treating neuropathic pain. In vivo patch-clamp recording is a useful procedure for analyzing the functional properties of synaptic transmission in SG neurons. Transient receptor potential ankyrin 1 (TRPA1) has been widely identified in the central and peripheral nervous systems, such as in the peripheral nociceptor, dorsal root ganglion, and spinal cord dorsal horn and is involved in synaptic transmission of pain. However, its functional role and mechanism of pain transmission in the spinal cord dorsal horn are not well understood. The purpose of this study was to use in vivo patch-clamp analysis to examine changes in the excitatory synaptic transmission of SG neurons treated with TRPA1 antagonist and to clarify the potential role of TRPA1 in the rat spinal cord dorsal horn.
  
  
  RESULTS
  The rats with root constriction (RC) showed mechanical hypersensitivity, hyperalgesia, and thermal hyperalgesia. In addition, pin pricks elicited pain-related behavior even in the sham and naïve rats. These pain-related behaviors were significantly attenuated by intrathecal injection of a TRPA1 antagonist. The degrees of intrathecal injection efficacy were equivalent among the 3 groups (RC, sham, and naïve groups). In an electrophysiological study, the frequencies and amplitudes of excitatory postsynaptic currents (EPSCs) were significantly increased in the RC rats compared with those in the sham and naïve rats. Spontaneous EPSCs and evoked-EPSCs by non-noxious and noxious stimuli were significantly decreased by TRPA1 antagonist. As in the behavioral study, there were no statistically significant differences among the 3 groups.
  
  
  CONCLUSIONS
  These data showed that the TRPA1 antagonist had an inhibitory effect on mechanical hypersensitivity and hyperalgesia as well as on physiological pain transmission in the spinal cord dorsal horn. This suggests that TRPA1 is consistently involved in excitatory synaptic transmission even in the physiological state and has a role in coordinating pain transmission.
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, S1 W16, Sapporo, Hokkaido 060-8543, Japan. tmiyakawa@sapmed.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Terashima
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Takebayashi
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Takehito
authors.initials: T
authors.lastname: Iwase
authors.forename: Izaya
authors.initials: I
authors.lastname: Ogon
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Tohse
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000083:Acetanilides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003250:Constriction; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006930:Hyperalgesia / Q000209:etiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D011843:Radiculopathy / Q000150:complications / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism*; D018709:Statistics, Nonparametric; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
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; D011687:Purines; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat