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Inhibition of SNL-induced upregulation of CGRP and NPY in the spinal cord and dorsal root ganglia by the 5-HT(2A) receptor antagonist ketanserin in rats.
Pharmacol Biochem Behav. 2012 May; 101(3):379-86.PB

Abstract

Our previous study has demonstrated that topical and systemic administration of the 5-HT(2A) receptor antagonist ketanserin attenuates neuropathic pain. To explore the mechanisms involved, we examined whether ketanserin reversed the plasticity changes associated with calcitonin gene-related peptides (CGRP) and neuropeptide Y (NPY) which may reflect distinct mechanisms: involvement and compensatory protection. Behavioral responses to thermal and tactile stimuli after spinal nerve ligation (SNL) at L5 demonstrated neuropathic pain and its attenuation in the vehicle- and ketanserin-treated groups, respectively. SNL surgery induced an increase in CGRP and NPY immunoreactivity (IR) in laminae I-II of the spinal cord. L5 SNL produced an expression of NPY-IR in large, medium and small diameter neurons in dorsal root ganglion (DRG) only at L5, but not adjacent L4 and L6. Daily injection of ketanserin (0.3 mg/kg, s.c.) for two weeks suppressed the increase in CGRP-IR and NPY-IR in the spinal cord or DRG. The present study demonstrated that: (1) the expression of CGRP was enhanced in the spinal dorsal horn and NPY was expressed in the DRG containing injured neurons, but not in the adjacent DRG containing intact neurons, following L5 SNL; (2) the maladaptive changes in CGRP and NPY expression in the spinal cord and DRG mediated the bioactivity of 5-HT/5-HT(2A) receptors in neuropathic pain and (3) the blockade of 5-HT(2A) receptors by ketanserin reversed the evoked upregulation of both CGRP and NPY in the spinal cord and DRG contributing to the inhibition of neuropathic pain.

Authors+Show Affiliations

Provincial Key Laboratory of Developmental Biology and Neuroscience, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, 350108, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22342663

Citation

Wang, Dongmei, et al. "Inhibition of SNL-induced Upregulation of CGRP and NPY in the Spinal Cord and Dorsal Root Ganglia By the 5-HT(2A) Receptor Antagonist Ketanserin in Rats." Pharmacology, Biochemistry, and Behavior, vol. 101, no. 3, 2012, pp. 379-86.
Wang D, Chen T, Gao Y, et al. Inhibition of SNL-induced upregulation of CGRP and NPY in the spinal cord and dorsal root ganglia by the 5-HT(2A) receptor antagonist ketanserin in rats. Pharmacol Biochem Behav. 2012;101(3):379-86.
Wang, D., Chen, T., Gao, Y., Quirion, R., & Hong, Y. (2012). Inhibition of SNL-induced upregulation of CGRP and NPY in the spinal cord and dorsal root ganglia by the 5-HT(2A) receptor antagonist ketanserin in rats. Pharmacology, Biochemistry, and Behavior, 101(3), 379-86. https://doi.org/10.1016/j.pbb.2012.02.004
Wang D, et al. Inhibition of SNL-induced Upregulation of CGRP and NPY in the Spinal Cord and Dorsal Root Ganglia By the 5-HT(2A) Receptor Antagonist Ketanserin in Rats. Pharmacol Biochem Behav. 2012;101(3):379-86. PubMed PMID: 22342663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of SNL-induced upregulation of CGRP and NPY in the spinal cord and dorsal root ganglia by the 5-HT(2A) receptor antagonist ketanserin in rats. AU - Wang,Dongmei, AU - Chen,Tingjun, AU - Gao,Yun, AU - Quirion,Rémi, AU - Hong,Yanguo, Y1 - 2012/02/09/ PY - 2011/11/29/received PY - 2012/02/01/revised PY - 2012/02/05/accepted PY - 2012/2/21/entrez PY - 2012/2/22/pubmed PY - 2012/8/3/medline SP - 379 EP - 86 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 101 IS - 3 N2 - Our previous study has demonstrated that topical and systemic administration of the 5-HT(2A) receptor antagonist ketanserin attenuates neuropathic pain. To explore the mechanisms involved, we examined whether ketanserin reversed the plasticity changes associated with calcitonin gene-related peptides (CGRP) and neuropeptide Y (NPY) which may reflect distinct mechanisms: involvement and compensatory protection. Behavioral responses to thermal and tactile stimuli after spinal nerve ligation (SNL) at L5 demonstrated neuropathic pain and its attenuation in the vehicle- and ketanserin-treated groups, respectively. SNL surgery induced an increase in CGRP and NPY immunoreactivity (IR) in laminae I-II of the spinal cord. L5 SNL produced an expression of NPY-IR in large, medium and small diameter neurons in dorsal root ganglion (DRG) only at L5, but not adjacent L4 and L6. Daily injection of ketanserin (0.3 mg/kg, s.c.) for two weeks suppressed the increase in CGRP-IR and NPY-IR in the spinal cord or DRG. The present study demonstrated that: (1) the expression of CGRP was enhanced in the spinal dorsal horn and NPY was expressed in the DRG containing injured neurons, but not in the adjacent DRG containing intact neurons, following L5 SNL; (2) the maladaptive changes in CGRP and NPY expression in the spinal cord and DRG mediated the bioactivity of 5-HT/5-HT(2A) receptors in neuropathic pain and (3) the blockade of 5-HT(2A) receptors by ketanserin reversed the evoked upregulation of both CGRP and NPY in the spinal cord and DRG contributing to the inhibition of neuropathic pain. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/22342663/Inhibition_of_SNL_induced_upregulation_of_CGRP_and_NPY_in_the_spinal_cord_and_dorsal_root_ganglia_by_the_5_HT_2A__receptor_antagonist_ketanserin_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(12)00039-1 DB - PRIME DP - Unbound Medicine ER -