Randall-Selitto test

Tests for modulation of nociception (also hot plate, Randall Selitto, tail pinch) Body temperature... 

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. 

The Randall-Selitto assay is a specific test for analgesia. In this test, a suspension of 20% brewer s yeast in water is injected into one hind foot of a rat. This causes an edematous condition that increases the rat s sensitivity to pain. The test compound is administered 2h after the yeast injection, and after an additional hour, the pain thresholds of the inflamed... 

This test, performed in rats, is the classical model of inflammatory pain. Intraplantar injection of inflammatory stimuli such as carrageenan, kaolin, or complete Freund adjuvants (CFA) induces paw swelling and increased pain sensitivity. As pain stimulus pressure is applied on the inflammed paw and gradually increased until the animal responds by vocalisation or withdrawal of the paw. Analgesics increase the pressure threshold (Randall and Selitto, Arch. Int. Pharmacodyn. 1957, 111, 409-419). 

Little is known about the mechanism of inflammatory pain. Kelly has discussed the question of pressure on nerves. The accumulation of exudate in an abscess leads to pain which is immediately relieved when the abscess is incised. On the other hand, greater tension exists in tissues affected by angioneurotic oedema although no pain is produced. It is known that externally-applied pressure, insufficient to elicit pain in normal tissue, causes pain in an inflamed area. Randall and Selitto used this hyperalgesic state as the basis for their now widely used test for analgesic drugs. 

In various analgesic tests phenylbutazone is active, though less so than amidopyrine . Clinically, however, it is of little value as an analgesic in pain of non-inflammatory origin . Randall and Selitto demonstrated a clear cut analgesic effect in inflammatory pain as measured by tolerance of pressure applied to the yeast-inflamed foot, a result which was confirmed by Crepax and Silvestrini . ... 

A series of substituted 1,3-diaryIbarbituric acids has been tested for antiinflammatory activity in the Randall and Selitto and pleural effusion tests. Some members are active but none approaches the potency of phenylbutazone . ... 

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