Formalin test

Interactions are seen between cocaine and the opioid system in analgesia. A synergistic effect occurs when cocaine is combined with a ju agonist (morphine) in the hot-plate test and a k agonist (U69,593) in the hot-plate test (Waddell and Holtzman 1999). Cocaine enhances morphine analgesia in several analgesic paradigms (e.g., formalin test, hot-plate test, and thermal tail-flick test)... 

Moss DE, Johnson RL. (1980). Tonic analgesic effects of delta 9-tetrahydrocannabinol as measured with the formalin test. EurJ Pharmacol. Feb. 8 61(3) 313-15. 

A.B. Malmberg, M.F. Rafferty, T.L. Yaksh, Antinociceptive effect of spinally delivered prostaglandin E receptor antagonists in the formalin test on the rat, Neurosci. Lett. 173 (1994) 193. 

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). 

Sawynok, J. and Reid, A. Antinociception by tricyclic antidepressants in the rat formalin test differential effects on different behaviours following systemic and spinal administration, Pain 2001, 93, 51-59. 

Sawynok, J., Reid, A. R., Esser, M. J. Peripheral antinociceptive action of amitriptyline in the rat formalin test involvement of adenosine, Pain 1999, 80, 45-55. 

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). 

Tran, M., Lufty, K., Xu, Z., Puthucode, R.N., Dimmock, J.R., Woodward, R.M. Antinocieceptive effects of Co102862, a novel anticonvulsant in tail flick and formalin tests in mice, Soc. Neurosci. Abstr. 1997, 23, 840.7. 

Therefore, it was surprising to find that retigabine had remarkable antihyperalgesic properties (as demonstrated by the dose-dependent inhibition of the second phase of the formalin test). Furthermore, it exerted a robust anti-allodynic effect in the chronic sciatic nerve constriction model of neuropathic pain (Rostock et al., 2000 Rundfeldt et al., 2001). The usefulness of retigabine and KCNQ2/3 channel openers in general for the treatment or prevention of chronic inflammatory and neuropathic pain has also been stressed by Burbidge et al. (2001). 

Formalin test Rat Nifedipine, Nimodipine, Verapamil, Diltiazem 1-30 mg/kg i-P- all drugs are active Miranda et al. (1992)... 

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. 

Concerning the -conopeptides, SNX-111 (Ziconotide) seems to be one of the proteins with the highest intrinsic antinociceptive activity in the formalin test (Table 4, Malmberg and Yaksh, 1994). This may be the main reason why most of the papers cited deal with this special synthetic peptide. 

In the tail flick assay -conotoxin GVIA in combination with morphine leads to an additive effect similar to the combination of morphine with SNX-111 in the formalin test. But when -conotoxin GVIA was applied 24 h before morphine, antinociception was greatly reduced. In morphine-dependent rats, w-conotoxin GVIA given i.c.v. 15 min before naloxone challenge (2 mg/kg i.p.), significantly attenuated the withdrawal symptoms (Table 4, Basilico et al., 1992). 

Formalin test (2nd phase) SNX-111 0.1 pg i.t. Suppression of nociceptive responses (flinch behavior) Bowersox et al. (1998)... 

Formalin test Morphine SNX-111 (Ziconotide) dose-response curves alone and in combination i.t. Isobolographical analysis combination of both drugs results in an additive effect Wang et al. (2000)... 

Bustamante, D., Miranda, H.F., Pelissier, T., Paeile, C. Analgesic action of clonixin, nifedipine and morphine using the formalin test, Gen. Pharmacol. 1989, 20, 319-322. 

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). 

Yashpal, K., Fisher, K., Chabot, J.-G., Coderre, T. J. Differential effects of NMDA and group I mGluR antogonists on both nociception and spinal cord protein kinase C translocation in the formalin test and a model of neuropathic pain in rats, Pain 2001, 94, 17-29. 

Lutfy, K., Shen, K.-Z., Woodward, R. M., Weber, E. Inhibition of morphine tolerance by NMDA receptor antagonists in the formalin test, Brain Res. 1996, 731, 171-181. 

Pharmacological investigations have proven J-113397 to be the most potent ORL1 antagonist known today (Ozaki et al., 2000a, b Bigoni et al., 2000 Ichikawa et al., 2001). J-113397 is reported to be active in the formalin test, but inactive against pain responses to thermal and mechanical stimuli (Okuda et al., 2000). 

Karlsten, R., Gordh, T., Post, C. Local antinociceptive and hyperalgesic effects in in the formalin test after peripheral administration of adenosine analogues in mice, Pharmacol. Toxicol 1992, 70, 434-438. 

Anandamide was shown to alleviate nociception in several behavioral animal models, e.g. the hot plate and formalin test (Calignano et al., 2001). A most interesting aspect of anandamide with respect to pain research is that it seems to bind to the hypothetical third cannabinoid receptor (Di Marzo et al., 2000b) In the hot plate test anandamide is still antinociceptive in CB/ mice, which is consistent with the observation that the selective CBi receptor antagonist SR 141716A does not block motor inhibitory and antinociceptive effects of anandamide in wild-type mice. 

Altier, N. and Stewart, J. The tachykinin NK-1 receptor antagonist, RP-67580, infused into the ventral tegmental area prevents stress-induced analgesia in the formalin test, Physiol. Behav. 1999, 66, 717-721. 

Formalin test A small amount of formalin solution is injected into the hind paw of mice or rats. This induces a bi-phasic pain reaction and a specific pain-related behaviour. The first phase represents acute nociceptive pain, whereas the second phase indicates more persistent pain associated with inflammation and tissue damage. Pain behaviour is observed in both phases and measured by means of a scoring system. Besides opioids, compounds active against inflammatory and neuropathic pain can be detected (Dubuisson and Dennis, Pain 1977, 4, 161-174). 

It must be mentioned, however, that intrathechal administration of IB-MECA does not exhibit an antinociceptive profile in acute nociception as assessed in the early phase pain response of the formalin test, but it does depress the late phase of... 

Yoon MH, Bae HB, Choi JI (2005) Antinociception of intrathecal adenosine receptor subtype agonists in rat formalin test. Anesth Analg 101 (5) 1417—1421... 

Tan-No, K., Taira, A., Sakurada, T., Inoue, M., Sakurada, S., Tadano, T., Sato, T., Sakurada, C., Nylander, I., Silberring, J., Terenius, L., and Kisara, K. (1996). Inhibition of dynorphin-converting enzymes prolongs the antinociceptive effect of intrathecally administered dynorphin in the mouse formalin test. Eur.J. Pharmacol. 314, 61-67. 

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