Distinct antinociceptive actions mediated by different opioid receptors in the region of lamina I and laminae III‐V of the dorsal horn of the rat

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Abstract
1 In view of the presence of μ, δ and κ opioid receptors in the spinal dorsal horn and their apparent involvement in behavioural analgesia, the present experiments addressed the action of selective agonists ionophoresed in the vicinity of rat dorsal horn neurones which were located either in lamina I or in laminae III‐V. 2 In laminae III‐V, κ agonists (U50488H and dynorphin A) caused a selective inhibition of the nociceptive responses of multireceptive cells, whilst μ and δ agonists ([d‐Ala2,MePhe4,Gry‐ol]enkephalin and [d‐Pen2,d‐Pen5]enkephalin respectively) failed to alter either the spontaneous activity or the responses to noxious and innocuous cutaneous stimuli and to d,l‐homocysteic acid or glutamate. Nocispecific neurones were encountered too rarely in laminae III‐V to study their properties. 3 In lamina I, agonists had no effects on either nocispecific or multireceptive neurones. In contrast, the μ agonist [d‐Ala2,MePhe4,Gly‐ol]enkephalin consistently inhibited nociceptive responses of both multireceptive and nocispecific lamina I cells. The δ agonist [d‐Pen2,d‐Pen5]enkephalin consistently caused selective inhibition of the nociceptive responses of multireceptive cells but had a mixed profile of action on nocispecific cells. 4 These results suggest that μ, δ and κ opioid receptors mediate different antinociceptive actions in both laminae III‐V and lamina I. The study reveals a distinct physiological role for δ receptors in modulating nociceptive inputs to lamina I neurones. In contrast to μ and κ receptor actions, δ receptors heterogeneously influence subpopulations of neurones.