Involvement of neuropeptide Y in the acute, chronic and withdrawal responses of morphine in nociception in neuropathic rats: behavioral and neuroanatomical correlates.

Abstract

Although morphine is a potent antinociceptive agent, its chronic use developed tolerance in neuropathic pain (NP). Furthermore, opioid antagonist naloxone attenuated the antinociceptive effect of neuropeptide Y (NPY). The present study investigated the role of NPY and NPY Y1/Y5 receptors in acute and chronic actions of morphine in neuropathic rats using thermal paw withdrawal test and immunocytochemistry. In acute study, intracerebroventricular (icv) administration of morphine, NPY or NPY Y1/Y5 receptors agonist [Leu(31),Pro(34)]-NPY produced antinociception, whereas selective NPY Y1 receptors antagonist BIBP3226 caused hyperalgesia. While NPY or [Leu(31),Pro(34)]-NPY potentiated, BIBP3226 attenuated morphine induced antinociception. Chronic icv infusion of morphine via osmotic minipumps developed tolerance to its antinociceptive effect, and produced hyperalgesia following withdrawal. However, co-administration of NPY or [Leu(31),Pro(34)]-NPY prevented the development of tolerance and withdrawal hyperalgesia. Sciatic nerve ligation resulted in significant increase in the NPY-immunoreactive (NPY-ir) fibers in ventrolateral periaqueductal gray (VLPAG) and locus coeruleus (LC); fibers in the dorsal part of dorsal raphe nucleus (DRD) did not respond. While chronic morphine treatment significantly reduced NPY-ir fibers in VLPAG and DRD, morphine withdrawal triggered significant augmentation in NPY-immunoreactivity in the VLPAG. NPY-immunoreactivity profile of LC remained unchanged in all the morphine treatment conditions. Furthermore, removal of sciatic nerve ligation reversed the effects of NP, increased pain threshold and restored NPY-ir fiber population in VLPAG. NPY, perhaps acting via Y1/Y5 receptors, might profoundly influence the processing of NP information and interact with the endogenous opioid system primarily within the framework of the VLPAG.

• Authors: Manoj A Upadhya, Manoj P Dandekar, Dadasaheb M Kokare, Praful S Singru, Nishikant K Subhedar
• Journal: Neuropeptides (Neuropeptides) Vol. 43 Issue 4 Pg. 303-14 (Aug 2009) ISSN: 1532-2785 [Electronic] Netherlands
• PMID: 19556004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• BIBP 3226
• Neuropeptide Y
• Receptors, Neuropeptide Y
• Morphine
• Arginine

Topics

• Analgesics, Opioid (therapeutic use)
• Animals
• Arginine (analogs & derivatives, metabolism)
• Behavior, Animal (physiology)
• Drug Tolerance
• Hyperalgesia (drug therapy, physiopathology)
• Male
• Morphine (therapeutic use)
• Neuropeptide Y (chemistry, metabolism)
• Pain Measurement
• Peripheral Nervous System Diseases (pathology, physiopathology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Receptors, Neuropeptide Y (agonists, antagonists & inhibitors, metabolism)
• Sciatic Nerve (pathology, physiopathology)
• Substance Withdrawal Syndrome (physiopathology)