Chronic pain model

Walpole, C., Ko, S. Y., Brown, M., Beattie, D., Campbell, E., Dickenson, F., Ewan, S., Hughes, G. A., Lemaire, M., Lerpiniere, J., Patel, S., Urban, L. 2-Nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide (SDZ NKT 343), a potent human NK1 tachykinin receptor antagonist with good oral analgesic activity in chronic pain models, J. Med. Chem. 1998b, 41, 3159-3173. 

The antinociceptive effects are produced by peripheral, spinal and supraspinal levels as well (Przewlocki et al., 1999). ICV or intrathalamic administration of EMs produced antinociception in both acute and chronic pain models (Zadina et al., 1997 Zhao et al., 2007 Zubrzycka et al., 2005 Zubrzycka and Janecka, 2008). The EMs displayed lower potencies in the mechanical (paw pressure) test than in the heat-pain (TE) test in rats after IT administration (Horvath et al., 1999 Przewlocka et al., 1999), but they exerted high analgesic potency in different inflammatory pain... 

Sandor K, Elekes K, Szabo A, Pinter E, Engstrom M, Wurster S, Szolcsanyi J, Helyes Z (2006) Analgesic effects of the somatostatin sst4 receptor selective agonist J-2156 in acute and chronic pain models. Eur J Pharmacol 539 71-75... 

Zhang J, Chen C (2008) Endocannabinoid 2-arachidonoylglycerol protects neurons by limiting COX-2 elevation. J Biol Chem 283 22601-22611 Zhang J, Hoffert C, Vu HK, Groblewski T, Ahmad S, O DonneU D (2003a) Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. EurJ Neurosci 17 2750-2754... 

Tramadol is a central-acting analgesic, effective for mild to moderate acute and chronic pain. It impairs nociception by a unique mechanism that is not completely understood. In animal models, it binds to the /u. opioid receptor and is a weak inhibitor of serotonin and norepinephrine reuptake, actions similar to those ascribed to the SSRIs and TCAs. Seizures have been reported in patients taking tramadol. Abuse potential is low, but does exist. 

Gurney ME, Fleck TJ, Himes CS, Hall ED (1998) Riluzole preserves motor fimction in a transgenic model of familiar amyotrophic lateral sclerosis. Neurology 50 62-67 Haines DR, Gaines SP (1999) N of 1 randomised controlled trials oforal ketamine in patients with chronic pain. Pain 83 283-287... 

The idea of reduced adrenal capacity as a possible model for PTSD has also been recently raised by Heim et ah, who concluded that low cortisol may not be a unique feature of PTSD, but may represent a more universal phenomenon related to bodily disorders, having an etiology related to chronic stress (Heim et al. 2000). There are numerous stress-related disorders such as chronic fatigue syndrome, fibromyalgia, rheumatoid arthritis, chronic pain syndromes, and other disorders that are characterized by hypocortisolism. In one study, Heim et al. showed decreased cortisol responses to low-dose DEX, but failed to observe blunted ACTH responses to CRF in women with chronic pelvic pain, some of whom had PTSD, compared to women with infertility (Heim et al. 1998). Since the data were not analyzed on the basis of the subgroup with and without trauma and/or PTSD, it is not possible to directly compare results of that study to other reports examining PTSD directly. 

In preclinical tests, antidepressants can also be effective in acute pain models, but in humans the acute analgesic effects are rather small and of no therapeutic relevance. When used as adjunctive treatment, usually doses lower than those required for the treatment of depression are sufficient for improvement of pain, reducing the side-effects arising from this adjunctive treatment. However, antidepressant treatment has clear beneficial effects only in a proportion of patients (McQuay and Moore, 1997) and may not be equally effective in all chronic pain states (Onghena and van Houdenhove, 1992). 

In preclinical studies, a number of TCAs (imipramine, amitriptyline, nortriptyline, desipramine) were shown to inhibit pain behavior in the formalin test after systemic as well as after i.t. administration, and this effect did not seem to be related to an antiinflammatory effect of these drugs (Sawynok and Reid, 2001). The effects of TCAs in preclinical acute pain models (involving acute thermal or mechanical stimuli) have been reviewed by Eschalier et al. (1999). TCAs were also active in models of chronic inflammation (Butler et al., 1985) and in models of neuropathic pain involving nerve injury (e.g. Ardid and Guilbaud, 1992 Abdi et al., 1998). 

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... 

Safinamide is a mixed Na+ and Ca2+ channel blocker with anticonvulsant, neuroprotective and anti-parkinsonian properties and is currently in phase II clincical trials for the indications epilepsy and Morbus parkinson (for review see Chazot, 2001). Additionally, analgesic activity has been shown in acute pain models (hot plate, tail flick) and more pronounced in a chronic, persistent pain model (formalin test) in mice in a dose range of 7.5 to 120 mg/kg p.o. (Salvati et al., 1999). 

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. 

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