No abstract

Results suggest that nSTZ leads to activation of SGC, microglia and astrocytes in DRG and spinal cord. Pharmacological profile in the nSTZ model resembles diabetic neuropathic pain in humans. Our findings support the conclusion that the nSTZ rat model has utility for the study of a long-lasting diabetic neuropathic pain.

Preclinical Research This work was performed to assess the effects of intrathecal serotonin 2B (5-HT ) receptor antagonists in rats with neuropathic pain. With RS-127445, its effect was also determined on 5-HT receptor expression. Neuropathic pain was induced by L5/L6 spinal nerve ligation. Western blotting was used to determine 5-HT receptor expression. Dose-response curves with the 5-HT receptor antagonists 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyridine (RS-127445, 1-100 nmol) and 1-[(2-chloro-3,4-dimethoxyphenyl)methyl]-2,3,4,9-tetrahydro-6-methyl-1H-pyrido[3,4-b]indole hydrochloride (LY-266097, 1-100 nmol) were performed in rats. Tactile allodynia of the left hind paw (ipsilateral) was assessed for 8 h after compound administration. Intrathecal injection of the 5-HT receptor antagonists RS-127445 and LY-266097 diminished spinal nerve ligation-induced allodynia. In contrast, intrathecal injection of the 5-HT receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 10 nmol) did not modify tactile allodynia induced by nerve ligation. L5/L6 nerve ligation increased expression of the 5-HT receptors in the ipsilateral, but not contralateral, dorsal root ganglia. Furthermore, nerve injury also enhanced 5-HT receptor expression in the ipsilateral dorsal part of the spinal cord. Intrathecal treatment with RS-127445 (100 nmol) diminished spinal nerve injury-induced increased expression of 5-HT receptors in dorsal root ganglia and spinal cord. Our results imply that spinal 5-HT receptors are present on sites related to nociception and participate in neuropathic pain. © 2014 Wiley Periodicals, Inc.

Transcription factors are proteins that modulate the transcriptional rate of target genes in the nucleus in response to extracellular or cytoplasmic signals. Activating transcription factors 2 (ATF2) and 3 (ATF3) respond to environmental signals and maintain cellular homeostasis. There is evidence that inflammation and nerve injury modulate ATF2 and ATF3 expression. However, the function of these transcription factors in pain is unknown. The purpose of this study was to investigate the contribution of ATF2 and ATF3 to nerve injury-induced neuropathic pain. L5/6 spinal nerve ligation induced tactile allodynia and thermal hyperalgesia. Moreover, nerve damage enhanced ATF2 and ATF3 protein expression in injured L5/6 dorsal root ganglia and spinal cord but not in uninjured L4 dorsal root ganglia. Nerve damage also enhanced ATF2 immunoreactivity in dorsal root ganglia and spinal cord 7 to 21 days post-injury. Repeated intrathecal post-treatment with a small-interfering RNA targeted against ATF2 (ATF2 siRNA) or anti-ATF2 antibody partially reversed tactile allodynia and thermal hyperalgesia. In contrast, ATF3 siRNA or anti-ATF3 antibody did not modify nociceptive behaviors. ATF2 immunoreactivity was found in dorsal root ganglia and spinal cord co-labeling with NeuN mainly in non-peptidergic (IB4+) but also in peptidergic (CGRP+) neurons. ATF2 was found mainly in small- and medium-sized neurons. These results suggest that ATF2, but not ATF3, is found in strategic sites related to spinal nociceptive processing and participates in the maintenance of neuropathic pain in rats.

Data suggest that AE3 is present in DRG and contributes to mechanical allodynia and thermal hyperalgesia in neuropathic rats.

Stress (195) Altered tropomysin receptor kinase B (TrkB) protein expression in the hypothalamus links to prolonged stress-induced enduring mechanical allodynia in na€ ıve and thermal injured rats