Chronic constriction injury

Chronic constriction injury (CCI) models (Bennett and Xie, 1988 Kim and Chung, 1992 Mosconi and Kruger, 1996) have been used to examine chronic pain states in experimental animals. In these models, intrathecally administered a2-agonists reduced mechanical allodynia and thermal hyperalgesia that developed following nerve constriction (Levy et al., 1994 Yaksh et al., 1995). This... 

Dib-Hajj, S. D., Fjell, J., Cummins, T. R., Zheng, Z., Fried, K., LaMotte, R. Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain, Pain 1999, 83, 591-600. 

Compounds with moderate p-affinities are very potent in a variety of pain models in mice and rats. In addition to antinociceptive efficacy in models of acute pain (tail flick, writhing) these compounds inhibit acute and persistent inflammatory pain (Randall Selitto, formalin test). Furthermore, they show strong inhibition of acute visceral pain (colorectal distension) and of tactile and cold allodynia in models of neuropathic pain (spinal nerve ligation (Chung), chronic constriction injury (Bennett)). The data suggest these compounds to be potential candidates for the management of clinical pain indications. Somatic and visceral pain with and without inflammatory conditions as well as neuropathic pain might be addressed with this approach. 

In contrast to its non-significant effects when administered i.t. in the formalin-test, i.t. treatment with (S)-4CPG was effective at significantly reducing neuropathic-like pain behavior in nerve-injured rats (Fisher et al., 1998 Yashpal et al., 2001 for a review see Fundytus, 2001). Consistent with the behavioural effects, there is evidence that chronic constriction injury induced increases in the translocation and activation of spinal PKC dependent on activity at mGlu1/5 receptors (Yashpal et al., 2001). 

The analgesic effect of NOS inhibitors refers to the inhibition of nNOS and, in the case of inflammation, iNOS. Knock-out experiments support this thesis mice lacking iNOS have a delay in the expression of neuropathic pain following a chronic constriction injury of nerves associated with neuropathic pain (Levy et al., 2001). For physiological changes observed in nNOS-, iNOS- and eNOS-knock-out mice, see Table 2. 

Kleinschnitz, C., Hofstetter, H. H., Meuth, S. G., Braeuninger, S., Sommer, C., and Stoll, G. (2006). T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression. Exp. Neurol. 200, 480-485. 

Lindenlaub, T., Teuteberg, P., Hartung, T., and Sommer, C. (2000). Effects of neutralizing antibodies to TNF-alpha on pain-related behavior and nerve regeneration in mice with chronic constriction injury. Brain Res. 866, 15—22. 

Okamoto, K., Martin, D. P., Schmelzer, J. D., Mitsui, Y., and Low, P. A. (2001). Pro- and antiinflammatory cytokine gene expression in rat sciatic nerve chronic constriction injury model of neuropathic pain. Exp. Neurol 169, 386-391. 

Ma F, Xie H, Dong ZQ, Wang YQ, Wu GC (2003) Effed of intratheceil nodstatin on nod-ceptin/orphanin FQ analgesia in chronic constriction injury rat. Brain Res 988 189—192 Ma QP, Bleasdale C (2002) Modulation of brain stem monoamines and gamma-aminobutyric acid by NKl receptors in rats. NeuroReport 13 1809-1812 Ma W, Eisenach JC (2007) Neuronal nitric oxide synthase is upregulated in a subset of primary sensory afferents after nerve injury which are necessary for analgesia from alpha2-adrenoceptor stimulation. Brain Res 1127 52-58... 

Wilson-Gerwing TD, Verge VMK (2006) Neurotrophin-3 attenuates galanin expression in the chronic constriction injury model of neuropathic pain. Neuroscience 141 2075-2085 Wirkner K, Sperlagh B, Hies P (2007) P2X(3) receptor involvement in pain states. Mol Neurobiol 36 165-183... 

Waxman There is a nagging issue of the apparently different results from different laboratories. One does an experiment as simple as cutting the sciatic nerve and looking for neuropathic hyperexcitability, but the results are very different from different laboratories. It is often because of different strains of rats or mice and different operators a chronic constriction injury in one lab may involve a tighter suture than in another laboratory, or there may be polymorphisms that hold some clues for us. It is important for us as investigators to look at the disparities and see whether we can even use them as tools. 

Schafers M, Geis C, Svensson C I, et al. (2003). Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Euro. J. Neurosci. 17 791-804. 

Okuda K, Takanishi T, Yoshimoto K, et al. Trazodone hydrochloride attenuates thermal hyperalgesia in a chronic constriction injury rat model. Ear Acad Anaesthesiol 2003 20 409-414. 

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