Peripheric antinociceptive effect

Rodrigues, A. R. A. and Duarte, I. D. G. The peripheral antinociceptive effect induced by morphine is associated with ATP-sensitive C channels, British Journal of Pharmacology 2000, 129, 110-114. 

Labuz D, Berger S, Mousa SA, ZoUner C, Rittner HL, Shaqura MA, Segovia-SUvestre T, Przewlocka B, Stein C, Machelska H (2006) Peripheral antinociceptive effects of exogenous and immune cell-derived endomorphins in prolonged inflammatory pain. J Neurosci 26 4350-4358... 

Reis GM, Duarte ID (2007) Involvement of chloride channel coupled GABA(C) receptors in the peripheral antinociceptive effect induced by GABA(C) receptor agonist cis-4-aminocrotonic acid. Life Sci 80 1268-1273... 

Obara I, Makuch W, Spetea M, Schiitz J, Schmidhammer H, Przewlocki R, Przewlocka B (2007) Local peripheral antinociceptive effects of 14-0-methyloxymorphone derivatives in inflammatory and neuropathic pain in the rat. Eur J Pharmacol 558 60-67... 

The writhing test, a model that permits an assessment of the peripheric antinociceptive effect of drugs by i.p. injection of formic acid, showed that S. desoleana oil possesses a remarkable analgesic effect comparable to the action of indomethacin, administered in the same experimental conditions. The action of S. desoleana oil seems to be attributable to its oxygenated components and is more intense than that of S. sclarea oil [35, 77]. 

Many anti-inflammatory aryl acids possess peripheral antinociceptive effects a ranking list of their relative analgesia in man and in animals has been compiled. Perhaps to a lesser degree, their antiinflammatory activity is also dependent on the CNS system in several assays. 

Findings continue to accumulate in the field of endogenous opiates, as exemplified by two tetrapeptides isolated from mammalian brain and found to have high affinity and selectivity for p-opioid receptors. These tetrapeptides are endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2). A number of synthetic analogues have been prepared with the view to improve their metabolic stability and, in some cases, to limit their access to peripheral opioid receptors. The three synthetic endomor-phin analogues Tyr-D-Ala-Phe-Phe-NH2 (6.84), Tyr-D-Arg-Phe-Phe-NH2 (6.85), and Tyr-D-Arg-Phe-Ape-NH2 (6.86), to be discussed in the next section, have potent antinociceptive effects in in vivo inflammatory tests but exhibit modest effects in the CNS. However, and despite the presence of a D-amino acid and a protected C-terminus, they remained sensitive to enzymatic hydrolysis [211][212],... 

Christensen, D., IdSnpSan-Heikkila, J. J., Guilbaud, G., Kayser V. The antinociceptive effect of combined systemic administration of morphine and the glycine/NMDA antagonist, (+)-HA-966 in a rat model of peripheral neuropathy, Br. J. Pharmacol. 1998, 125, 1641-1650. 

Marubio et al., 1999 Williams et al., 1999). This speculation is corroborated by data suggesting that only neuronal nAChRs are important for the antinociceptive effects of epibatidine, while toxic effects might be mediated by peripheral nAChRs (Sullivan et al., 1994). 

Epibatidine s antinociceptive effect can be antagonized by pretreatment with the centrally active nAChR antagonist mecamylamine, but not with the peripheral antagonist hexamethonium, so the activation of central nAChRs is presumed to be essential for nicotinic analgesics (Sullivan et al., 1994). The high toxicity of epibatidine has been attributed to its lack of selectivity for specific neuronal nAChR subtypes and has precluded its development as a therapeutic agent. 

Moreover, duration of central NKi receptor blockade is a critical point, as anesthetic-like nerve block caused by non-specific effects on ion channels in peripheral tissues could mask the selective antinociceptive effects of blocking NKi receptors in the spinal cord. The long-acting NKi antagonist L-733,060 maintained blockade of central NKi receptors at a time when peak plasma drug levels had subsided. Therefore, in paw licking experiments, the inhibitory effect of L-733,060 appeared to be due to central NKi receptor blockade (Rupniak et al., 1996). 

NKi receptor antagonists exhibit weak potency in acute pain, whereas antinociceptive effects can only be observed after persistent peripheral inflammation, i.e. models of chronic pain (Radhakrishnan et al., 1998 Saria, 1999). This view has been confirmed with the discovery of the even more selective SDZ NKT343, mentioned above (Walpole et al., 1998a,b). 

Since the discovery and characterization of P-endorphin (31 amino acids) as an opioid peptide in 1976, the opinion has been widely held that this peptide has a role in the control of pain (Akil et al., 1984 Basbaum and Fields, 1984 Loh et al 1976 Rossier et al., 1977). POMC-derived P-endorphin is considered to be a key component of the endogenous antinociceptive system attenuating the stress- and inflammation-induced hyperalgesia (Rossier et al., 1977 Stein et al., 1990 Sun et al., 2003). It binds with high affinity to both MOR and DOR (Akil et al., 1984). Pain stimulation induces PAG release of 3-endorphin and the ICV administration of 3-endorphin produces analgesia (Akil et al., 1984). Similarly, both spinal and peripheral administration of 3-endorphin evokes antinociceptive effects in different pain models (Chung et al., 1994 Stein et al., 1990 Suh et al., 1994 Suh et al.,... 

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... 

Dirig DM, Yaksh TL (1995) Intrathecal baclofen and muscimol, but not midazolam, are antinociceptive using the rat-formahn model. J Pharmacol Exp Ther 275 219-227 Dirig DM, Yaksh TL (1999) In vitro prostanoid release from spinal cord following peripheral inflammaton effects of substance P, NMDA and capsaicin. Br J Pharmacol 126 1333-1340... 

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