Differential association of spinal μ, δ and κ opioid receptors with cutaneous thermal and visceral chemical nociceptive stimuli in the rat

Abstract The intrathecal administration of several μ (morphine), δ (d-ala 2 -d-leu 5 -enkephalin, dimeric leu-enkephalin) and mixed μ/σ (β-endorphin) agonists produced a dose-dependent inhibition of all cutaneous thermal (Tail Flick/Hot Plate) nociceptive responses in the rat. The κ agonist U50488H had no analgesic potency in thermal nociceptive tests. On a visceral chemical test (writhing) and agonists exerted a powerful suppression of the response. In contrast at doses 10 to 50 times the ED 50 on cutaneous thermal tests, δ agonists had no effect on the writhing response. At higher intrathecal doses, δ ligands produced flaccidity. These observations suggest the existence of three discriminable populations of opioid receptors in the spinal cord whose activation has different effects on the animals response to noxious stimuli.