2. Academic Validation
  3. Involvement of Rac1 signalling pathway in the development and maintenance of acute inflammatory pain induced by bee venom injection

Involvement of Rac1 signalling pathway in the development and maintenance of acute inflammatory pain induced by bee venom injection

  • Br J Pharmacol. 2016 Mar;173(5):937-50. doi: 10.1111/bph.13413.
Yan Wang 1 2 3,  Yun-Fei Lu 1 2 3,  Chun-Li Li 1 2 3,  Wei Sun 1 2 3,  Zhen Li 1 2 3,  Rui-Rui Wang 1 2 3,  Ting He 1 2 3,  Fan Yang 1 2 3,  Yan Yang 1 2 3,  Xiao-Liang Wang 1 2 3,  Su-Min Guan 4,  Jun Chen 1 2 3 5
Affiliations

Affiliations

  • 1 Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
  • 2 Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
  • 3 Key Laboratory of Brain Stress and Behavior, PLA, Xi'an, 710038, China.
  • 4 School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
  • 5 Beijing Institute for Brain Disorders, Beijing, 100069, China.
PMID: 26700000 DOI: 10.1111/bph.13413
Abstract

Background and purpose: The Rho GTPase, Rac1, is involved in the pathogenesis of neuropathic pain induced by malformation of dendritic spines in the spinal dorsal horn (sDH) neurons. In the present study, the contribution of spinal Rac1 to peripheral inflammatory pain was studied.

Experimental approach: Effects of s.c. bee venom (BV) injection on cellular localization of Rac1 in the rat sDH was determined with double labelling immunofluorescence. Activation of Rac1 and its downstream effector p21-activated kinase (PAK), ERKs and p38 MAPK in inflammatory pain states was evaluated with a pull-down assay and Western blotting. The preventive and therapeutic analgesic effects of intrathecal administration of NSC23766, a selective inhibitor of Rac1, on BV-induced spontaneous nociception and pain hypersensitivity were investigated.

Key results: Rac1 labelling was mainly localized within neurons in both the superficial and deep layers of the sDH in rats of naïve, vehicle-treated and inflamed (BV injected) groups. GTP-Rac1-PAK and ERKs/p38 were activated following s.c. BV injection. Post-treatment with intrathecal NSC23766 significantly inhibited GTP-Rac1 activity and phosphorylation of Rac1-PAK, ERKs and p38 MAPK in the sDH. Both pre-treatment and post-treatment with intrathecal NSC23766 dose-dependently attenuated the paw flinches, primary thermal and mechanical hyperalgesia and the mirror-image thermal hyperalgesia induced by BV injection, but without affecting the baseline pain sensitivity and motor coordination.

Conclusions and implications: The spinal GTP-Rac1-PAK-ERK/p38MAPK signalling pathway is involved in both the development and maintenance of peripheral inflammatory pain and can be used as a potential molecular target for developing a novel therapeutic strategy for clinical pain.

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