Neuropathic pain models

In addition, Novartis filed a patent application on a series of quinazolines as cannabinoid agonists [209]. Compound (320) is one of the two compounds specifically claimed and exhibited CBi and CB2 binding with if values of 34 and 11 nM, respectively. It was shown to be a full agonist at the CBi receptor with an EC50 of 132nM (no functional data for the CB2 receptor). Compound (320) was also active in the neuropathic pain model described above with an ED50 of 0.5mg/kg after oral dosing. 

Rostock, A., Rundfeldt, C., Bartsch, R. Effects of the anticonvulsant retigabine in neuropathic pain models in rats Poster presentation, 41st Annual Meeting of the German Society of Pharmacology and Toxicology 2000... 

Animal models of nociception can be divided according to the therapeutic indication Acute Pain, Migraine Pain, Inflammatory Pain, Visceral Pain, Neuropathic Pain. Different degrees of chronification (up to weeks in neuropathic pain models) and different stimuli (mechanical, thermal, chemical, electrical) are used depending on the experimental question. In most cases a nociceptive threshold (e g. withdrawal latency of a paw) is determined. Sometimes, nociceptive intensities are determined e.g. in order to quantify hyperalgesia. 

We expected that (-)-TAN-67 will be used for the detailed investigation of both the existence and the pharmacological effects of a <5i opioid receptor, and that the (+)-TAN-67-induced nociception may be a unique pharmacological model for the elucidation of pain mechanisms. Moreover, the hyperalgesia produced by (+)-TAN-67 could be one of the neuropathic pain models. We hope that the (+)-TAN-67-induced nociception will be used for the development of analgesics for neuropathic pain, for which morphine indicates little or no effect. 

Luo, Z. D., Calcutt, N. A., Higuera, E. S., Valder, C. R., Song, Y. H., Svensson, C. I., and Myers, R. R. (2002). Injury type-specific calcium channel alpha 2 delta-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J. Pharmacol. Exp. Ther. 303, 1199-1205. 

Lynch, J. J. 3rd, Wade, C. L., Zhong, C. M., Mikusa, J. P., and Honore, P. (2004). Attenuation of mechanical allodynia by clinically utilized drugs in a rat chemotherapy-induced neuropathic pain model. Pain 110, 56—63. 

Sakaue, G., Shimaoka, M., Fukuoka, T., Hiroi, T., Inoue, T., Hashimoto, N., Sakaguchi, T., Sawa, Y., Morishita, R., Kiyono, H., Noguchi, K., and Mashimo, T. (2001). NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model. 

Tegeder, I., Niederberger, E., Schmidt, R., Kunz, S., Guhring, H., Ritzeler, O., Michaelis, M., and Geisslinger, G. (2004). Specific Inhibition of IkappaB kinase reduces hyperalgesia in inflammatory and neuropathic pain models in rats. J. Neurosci 24, 1637—1645. 

The responses of animal chronic neuropathic pain models to opioid treatment have often not mirrored this opioid resistance observed in clinic and thus the results have been controversial. Some researchers have found that opioids may... 

In contrast, some data suggest that P2Y receptor agonists can inhibit cytokine release from aetivated spinal cord microglia (Gerevich and Illes, 2004). This process could interrupt chronic pain development and continuation. Thus, UTP and UDP were shown to be analgesic in the neuropathic pain model (Okada et al., 2002). IT pyrimidine nucleotides elevated the nociceptive threshold in the paw pressure and... 

Hwang JH, Yaksh TL (1997) The effect of spinal GABA receptor agonists on tactile aUodynia in a surgically-induced neuropathic pain model in the rat. Pain 70 15-22 Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata HP, Malan TP Jr (2005) CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sd U S A 102 3093-3098... 

Joseph T, Lee TL, Li C, Siau C, Nishiuchi Y, Kimura T, Tachibana S (2007) Levels of neuropeptides nocistatin, nociceptin/orphanin FQ and their precursor protein in a rat neuropathic pain model. Peptides 28 1433-1440... 

Moon DE, Lee DH, Han HC, Xie J, CoggeshaU RE, Chung JM (1999) Adrenergic sensitivity of the sensory receptors modulating mechanical aUodynia in a rat neuropathic pain model. Pain... 

Okada M, Nakagawa T, Minami M, Satoh M (2002) Antilgesic effects of intrathecal administration of P2Y nucleotide receptor agonists DTP and UDP in normtil and neuropathic pain model rats. J Pharmacol Exp Ther 303 66-73... 

Yamamoto T, Saito O, Shono K, Aoe T, Chiba T (2003) Anti-mechanical aUodynic effect of intrathecal and intracerebroventricular injection of orexin-A in the rat neuropathic pain model. Neurosci Lett 347 183-186... 

Oh E J, Yoon Y W, Lee S E, et al. (2000). Changes in nerve growth factor levels in dorsal root ganglia and spinal nerves in a rat neuropathic pain model. Exper. Brain Res. 130 93-99. 

Linalool, a monoterpene alcohol that is present in many EOs, was evaluated by Batista et al. (2010) for its antinociceptive effects using a neuropathic pain model. It sign cantly decreased the paw withdrawal response, and so it showed potent antinociceptive effects. 

---