title: Contribution of injured and uninjured dorsal root ganglion neurons to pain behavior and the changes in gene expression following chronic constriction injury of the sciatic nerve in rats.
abstract: Neuropathic pain models, such as the chronic constriction injury (CCI) model, are partial nerve injury models where there exist both intact and injured peripheral axons. Recent studies suggested that dorsal root ganglion (DRG) neurons with intact axons also show the alteration of excitability and gene expression and might have some role in the pathophysiological mechanisms of neuropathic pain. The incidence of pain-related behavior after the CCI is unstable and variable. In the present study, we used activating transcription factor 3 (ATF3) expression as a neuronal injury marker, and analyzed a relationship between the number of axotomized neurons and the incidence of pain-related behavior. We divided all rats into three groups according to the percentage of ATF3-immunoreactive (IR) neurons, group 1 (<12.5%), group 2 (12.5-25%), and group 3 (>25%). We found that rats in groups 2 and 3 showed thermal hyperalgesia, whereas only the rats in group 2 developed tactile allodynia from the third day to the fourteenth day after surgery. Rats in group 1 did not show thermal hyperalgesia or tactile allodynia. The DRG neurons in group 2 contained ATF3-IR neurons mainly in medium- and large-sized neurons. In order to investigate brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid(A)-receptor (GABA(A)-R) regulation in both intact and injured primary afferent neurons after the CCI, we used a double-labeling method with immunohistochemistry and in situ hybridization, as well as double immunofluorescent staining. The CCI induced an increased number of BDNF-labeled neurons in the ipsilateral DRG and the increase in BDNF expression was observed mainly in small- and medium-sized neurons that were mainly ATF3-negative. On the other hand, the number of GABA(A)-Rgamma2 subunit mRNA-positive neurons decreased in the ipsilateral DRG and GABA(A)-R- and ATF3-labeled neurons rarely overlapped. These changes in molecular phenotype in intact and injured primary afferents may be involved in the pathophysiological mechanisms of neuropathic pain produced by partial nerve injury.
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Obata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fukuoka
authors.forename: Dai
authors.initials: D
authors.lastname: Yi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tokunaga
authors.forename: Norio
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Noguchi
mesh_terms: D051700:Activating Transcription Factor 3; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics; D002908:Chronic Disease; D005727:Ganglia, Spinal / Q000166:cytology / Q000293:injuries*; D015870:Gene Expression; D006930:Hyperalgesia / Q000453:epidemiology / Q000503:physiopathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015994:Incidence; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000032:analysis / Q000235:genetics; D012585:Sciatica / Q000453:epidemiology / Q000503:physiopathology*; D014110:Touch; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014157:Transcription Factors