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There is evidence that post-injury hypersensitivity is partly due to changes in the central nervous system. Sheep with footrot were used to investigate the effect of chronic pain on some receptors thought to be involved in spinal nociceptive processing systems (alpha2 adrenoceptor and mu and delta opioid receptors).Saturation binding studies showed a variable distribution of [3H] clonidine (alpha2 adrenoceptor agonist) in the spinal cord of normal sheep. The number of receptors (Bmax) present in areas thought to be involved in nociceptive processing, laminae I and II and lamina X, increased to 131% and 169% of control sheep values respectively in animals exposed to chronic pain. The affinity of the receptors (KD), however, remained unchanged at approximately 2 nM. There was less [3H]DAGO (mu opioid agonist) and [3H]DPDPE (delta opioid agonist) binding in the sheep spinal cord. Both opioid receptor types being mainly located in the superficial dorsal horn. The [3H]DPDPE binding was unchanged in the sheep with footrot, whilst the number (Bmax), but not the affinity, of the [3H]DAGO binding sites increased in laminae I and II in lame animals to 130% of the control sheep values.Hence, in animals in chronic pain, the number of alpha2 adrenoceptors and mu opioid receptors increased mainly in areas of the sheep spinal cord associated with nociception.