Tonic Modulation of Nociceptive Behavior and Allodynia by Cannabinoid Receptors in Formalin Test in Rats

10.4077/CJP.2015.BAD307

Tian-Cheng Wang；Jing Wang；Xu Xu；Jing-Lin Ma；Xue-Feng Wang

allodynia ； cannabinoid receptor ； formalin test ； inflammatory pain ； rat ； tonic modulation

The Chinese Journal of Physiology

58卷1期（2015 / 02 / 01）

72 - 78

英文

Cannabinoids produce anti-nociceptive and anti-hyperalgesic effects in acute, inflammatory and neuropathic pain models. The current study investigated the role of cannabinoid (CB1 and CB2) receptors in modulating formalin-induced nociceptive behavior and mechanical allodynia in the rat. Rats received subcutaneous plantar injections of 5% formalin in the hind paws. Licking, biting and paw flinching nociceptive behaviors were measured 0-60min after formalin injection. Allodynia was measured at 3 and 6 h, and 1, 3, 5 and 7 days post-injection using the mechanical paw withdrawal threshold. Animals in the experimental group were given i.p. injections of CB1 and CB2 receptor antagonists AM281 and AM630 at a dose of 1mg/kg concomitant with formalin, and then twice daily for the following 7 days. AM281 and AM630 enhanced nociceptive behaviors, and attenuated the bilateral mechanical paw withdrawal threshold, compared with the vehicle. The results indicate that CB1 and CB2 receptors mediate a tonically inhibitory action on formalin-induced inflammatory pain, especially long-term allodynia, in bilateral hind paws.

1. Tsai, W.H.,Li, I.T.,Yu, Y.B.,Hsu, H.C.,Shih, C.H.(2014).Serial changes in plasma annexin A1 and cortisol levels in sepsis patients..Chinese J. Physiol,57,1-7.
   連結：
2. Wu, W.C.,Wang, Y.,Chai, C.Y.(2008).Acute effects of the cannabinoid receptor agonist WIN55212-2 on dopamine release in rat: anin vivo electrochemical study..Chinese J. Physiol,51,152-159.
   連結：
3. Agarwal, N.,Pacher, P.,Tegeder, I.,Amaya, F.,Constantin, C.E.,Brenner, G.J.,Rubino, T.,Michalski, C.W.,Marsicano, G.,Monory,K.,Mackie, K. Marian, C.,Batkai, S.,Parolaro, D.,Fischer, M.J.,Reeh, P.,Kunos, G.,Kress, M.,Lutz, B.,Woolf, C.J.,Kuner, R.(2007).Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors.Nat. Neurosci,10,870-879.
4. Alkaitis, M.S.,Solorzano, C.,Landry, R.P.,Piomelli, D.,DeLeo, J.A.,Romero-Sandoval, E.A.(2010).Evidence for a role of endocannabinoids,astrocytes and p38 phosphorylation in the resolution of postoperative pain..PLoS One,5,e10891.
5. Bai, Z.T.,Liu, T.,Jiang, F.,Cheng, M.,Pang, X.Y.,Hua, L.M.,Shi, J.,Zhou, J.J.,Shu, X.Q.,Zhang, J.W.,Ji, Y.H(2010).Phenotypes and peripheral mechanisms underlying inflammatory pain-related behaviors induced by BmK I, a modulator of sodium channels..Exp. Neurol.,226,159-172.
6. Barrot, M.(2012).Tests and models of nociception and pain in rodents.Neuroscience,211,39-50.
7. Beaulieu, P.,Bisogno, T.,Punwar, S.,Farquhar-Smith, W.P.,Ambrosino, G.,Di Marzo, V.,Rice, A.S.(2000).Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat..Eur. J. Pharmacol,396,85-92.
8. Borsani, E.,Labanca, M.,Bianchi, R.,Rodella, L.F.(2007).AM404 decreases Fos-immunoreactivity in the spinal cord in a model of inflammatory pain.Brain Res,1152,87-94.
9. Butler, R.K.,Rea, K.,Lang, Y.,Gavin, A.M.,Finn, D.P.(2008).Endocannabinoid-mediated enhancement of fear-conditioned analgesia in rats: opioid receptor dependency and molecular correlates.Pain,140,491-500.
10. Calignano, A.,La Rana, G.,Giuffrida, A.,Piomelli, D.(1998).Control of pain initiation by endogenous cannabinoids..Nature,394,277-281.
11. Chaplan, S.R.,Bach, F.W.,Pogrel, J.W.,Chung, J.M.,Yaksh, T.L.(1994).Quantitative assessment of tactile allodynia in the rat paw.J. Neurosci. Methods,53,55-63.
12. Costa, B.,Siniscalco, D.,Trovato, A.E.,Comelli, F.,Sotgiu, M.L.,Colleoni, M.,Maione, S.,Rossim, F.,Giagnoni, G.(2006).AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain..Brit. J. Pharmacol,148,1022-1032.
13. Froger, N.,Orellana, J.A.,Cohen-Salmon, M.,Ezan, P.,Amigou, E.,Sáez, J.C.,Giaume, C.(2009).Cannabinoids prevent the opposite regulation of astroglial connexin43 hemichannels and gap junction channels induced by pro-inflammatory treatments.J. Neurochem.,111,1383-1397.
14. Fu, K.Y.,Light, A.R.,Maixner, W.(2001).Long-lasting inflammation and long-term hyperalgesia after subcutaneous formalin injection into the rat hindpaw.J. Pain,2,2-11.
15. Guindon, J.,Desroches, J.,Beaulieu, P.(2007).The antinociceptive effects of intraplantar injections of 2-arachidonoyl glycerol are mediated by cannabinoid CB2 receptors..Brit. J. Pharmacol,6,693-701.
16. Hohmann, A.G.,Suplita, R.L.,Bolton, N.M.,Neely, M.H.,Fegley, D.,Mangieri, R.,Krey, J.F.,Walker, J.M.,Holmes, P.V.,Crystal, J.D.,Duranti, A.,Tontini, A.,Mor, M.,Tarzia, G.,Piomelli, D.(2005).An endocannabinoid mechanism for stress-induced analgesia.Nature,7045,1108-1112.
17. Iball, J.,Ali, A.B.(2011).Endocannabinoid Release Modulates Electrical Coupling between CCK Cells Connected via Chemical and Electrical Synapses in CA1.Front. Neural Circuits,17,1-12.
18. Jaggar, S.I.,Hasnie, F.S.,Sellaturay, S.,Rice, A.S.(1998).The antihyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain.Pain,1-2,189-199.
19. Kidd, B.L.,Urban, L.A.(2001).Mechanisms of inflammatory pain.Brit. J. Anaesth.,1,3-11.
20. Kinsey, S.G.,Long, J.Z.,O'Neal, S.T.,Abdullah, R.A.,,Poklis, J.L.,Boger, D.L.,Cravatt, B.F.,Lichtman, A.H.(2009).Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain..J. Pharmacol. Exp. Ther,3,902-910.
21. La Rana, G.,Russo, R.,Campolongo, P.,Bortolato, M.,Mangieri, R.A.,Cuomo, V.,Iacono, A.,Raso, G.M.,Meli, R.,Piomelli, D.,Calignano, A.(2006).Modulation of neuropathic and inflammatory pain by the endocannabinoid transport inhibitor AM404 [N-(4- hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide]..J. Pharmacol.Exp. Ther.,3,1365-1371.
22. Milligan, E.D.,Twining, C.,Chacur, M.,Biedenkapp, J.,O'Connor, K.,Poole, S.,Tracey, K.,Martin, D.,Maier, S.F.,Watkins, L.R.(2003).Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats..J. Neurosci,3,1026-1040.
23. Qin, M.,Wang, J.J.,Cao, R.,Zhang, H.,Duan, L.,Gao, B.,Xiong, Y.F.,Chen, L.W.,Rao, Z.R.(2006).The lumbar spinal cord glial cells actively modulate subcutaneous formalin induced hyperalgesia in the rat.Neurosci. Res,55,442-450.
24. Racz, I.,Nadal, X.,Alferink, J.,Baños, J.E.,Rehnelt, J.,Martín, M.,Pintado, B.,Gutierrez-Adan, A.,Sanguino, E.,Manzanares, J.,Zimmer, A.,Maldonado, R.(2008).Crucial role of CB2 cannabinoid receptor in the regulation of central immune responses during neuropathic pain.J. Neurosci,46,12125-12135.
25. Romero-Sandoval, A.,Nutile-McMenemy, N.,DeLeo, J.A.(2008).Spinal microglial and perivascular cell cannabinoid receptor type 2 activation reduces behavioral hypersensitivity without tolerance after peripheral nerve injury.Anesthesiology,4,722-734.
26. Sorkin, L.S.,Boyle, D.L.,Hammaker, D.,Herman, D.S.,Vail, E.,Firestein, G.S.(2009).MKK3, an upstream activator of p38, contributes to formalin phase 2 and late allodynia in mice.Neuroscience,2,462-471.
27. Spataro, L.E.,Sloane, E.M.,Milligan, E.D.,Wieseler-Frank, J.,Schoeniger, D.,Jekich, B.M.,Barrientos, R.M.,Maier, S.F.,Watkins, L.R.(2004).Spinal gap junctions: potential involvement in pain facilitation..J. Pain,7,392-405.
28. Sweitzer, S.M.,Colburn, R.W.,Rutkowski, M.,DeLeo, J.A.(1999).Acute peripheral inflammation induces moderate glial activation and spinal IL-1β expression that correlates with pain behavior in the rat.Brain Res,829,209-221.
29. Vierck, C.J.,Yezierski, R.P.,Light, A.R.(2008).Long-lasting hyperalgesia and sympathetic dysregulation after formalin injection into the rat hind paw..Neuroscience,2,501-506.
30. Walker, K.,Fox, A.J.,Urban, L.A.(1999).Animal models for pain research.Mol. Med. Today,7,319-321.
31. Watson, G.S.,Sufka, K.J.,Coderre, T.J.(1997).Optimal scoring strategies and weights for the formalin test in rats.Pain,1,53-58.
32. Xie, Y.F.,Wang, J.,Huo, F.Q.,Jia, H.,Tang, J.S.(2005).Validation of a simple automated movement detection system for formalin test in rats..Acta Pharmacol. Sin.,1,39-45.
33. Zimmermann, M.(1983).Ethical guidelines for investigations of experimental pain in conscious animals.Pain,2,109-110.