Characterization of scratching responses in rats following centrally administered morphine or bombesin

Abstract

The aim of this study was to characterize scratching behavior elicited by central administration of morphine or bombesin in rats, and to determine the role of opioid receptors in scratching induced by both pruritogenic agents. Central administration included intracisternal (i.c.), intrathecal (i.t.), and intracerebroventricular (i.c.v.) routes. Scratching events made with hind paws were counted by observers blinded to treatment conditions. Intracisternal morphine (0.01-0.1 μg) produced dosedependent increases in scratching; the maximum response to i.c. morphine 0.1 μg was approximately 500 scratches within a 1-hour period. Neither i.t. nor i.c.v. morphine significantly increased scratching. Bombesin (0.01 -0.32 μg) elicited robust scratching following i.c. administration. The maximum response to i.c. bombesin 0.32 μg was approximately 4000 scratches within a 1-hour period. Both i.t. and i.c.v. bombesin produced profound scratching at similar doses. Antagonist studies confirmed that mu-opioid receptors selectively mediate i.c. morphine-induced scratching. However, selective mu-, kappa-, and delta-opioid antagonists did not attenuate i.c. bombesin-induced scratching. These results demonstrate that morphine and bombesin elicit scratching through different receptor mechanisms, at different central sites, and to different degrees.

Effects of Atypical κ-Opioid Receptor Agonists on Intrathecal Morphine-Induced Itch and Analgesia in Primates

“…An early study has shown that subcutaneous administration of nalfurafine could effectively suppress intracisternal morphine-induced scratching in mice (Umeuchi et al, 2003). However, as previously demonstrated, intrathecal morphine simultaneously produces both scratching and antinociception in monkeys, but not in rodents (Ko and Naughton, 2000;Ko et al, 2003a;Lee et al, 2003). The present study of KOR agonists as antipruritics in primates further extends the therapeutic application of KOR agonists under the context of spinal opioid analgesia (Ko et al, 2003a;Lee et al, 2007; the present study).…”

Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics

“…22,24 However, ultra low doses of N/OFQ administered intrathecally at the dose range of femtomoles produced spontaneous agitation and pain manifested by biting, scratching, and licking behavioral Available online at www.sciencedirect.com responses in mice, suggesting that spinal N/OFQ has biphasic actions in rodents. 15,40 Anatomical studies indicated that species differences may exist in the distribution of N/OFQ and NOP receptors.…”

“…22 Such naltrexone-insensitive effects could be blocked by the selective N/OFQ peptide receptor (NOP) antagonist J-113397 indicating that activation of spinal NOP receptors may be a promising target for spinal analgesia. 22,24 However, ultra low doses of N/OFQ administered intrathecally at the dose range of femtomoles produced spontaneous agitation and pain manifested by biting, scratching, and licking behavioral responses in mice, suggesting that spinal N/OFQ has biphasic actions in rodents. 15,40 Anatomical studies indicated that species differences may exist in the distribution of N/OFQ and NOP receptors.…”

“…Interestingly, such unique effects of intrathecal morphine in humans [2,31] can be modeled in monkeys, but not in rodents, as a single dose of morphine produced both antinociception and itch/scratching responses simultaneously in monkeys [17,20,24]. For studying opioid analgesics in vivo, the scratching response can be used as a selective behavioral endpoint corresponding to activation of MOP [18,25].…”

“…The therapeutic potential of N/ OFQ and the NOP receptors has been emphasized for its broad medical applications. 24,45 Given that intrathecal N/OFQ produces antinociception without eliciting itch/ scratching responses in monkeys, N/OFQ or other NOP receptor agonists represent a viable target as spinal analgesics for future clinical trials. …”