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Abstract
<p class="first" id="d9127283e59">The formalin test in mice is a valid and reliable
model of nociception and is sensitive
for various classes of analgesic drugs. The noxious stimulus is an injection of dilute
formalin (1% in saline) under the skin of the dorsal surface of the right hindpaw.
The response is the amount of time the animals spend licking the injected paw. Two
distinct periods of high licking activity can be identified, an early phase lasting
the first 5 min and a late phase lasting from 20 to 30 min after the injection of
formalin. In order to elucidate the involvement of inflammatory processes in the two
phases, we tested different classes of drugs in the two phases independently. Morphine,
codeine, nefopam, and orphenadrine, as examples of centrally acting analgesics, were
antinociceptive in both phases. In contrast, the non-steroid anti-inflammatory drugs
indomethacin and naproxen and the steroids dexamethasone and hydrocortisone inhibited
only the late phase, while acetylsalicylic acid (ASA) and paracetamol were antinociceptive
in both phases. The results demonstrate that the two phases in the formalin test may
have different nociceptive mechanisms. It is suggested that the early phase is due
to a direct effect on nociceptors and that prostaglandins do not play an important
role during this phase. The late phase seems to be an inflammatory response with inflammatory
pain that can be inhibited by anti-inflammatory drugs. ASA and paracetamol seem to
have actions independent of their inhibition of prostaglandin synthesis and they also
have effects on non-inflammatory pain.
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