Background & Aims

Opioids like morphine are the mainstay in the treatment of pain. However,
development of tolerance to its antinociceptive effect limits its use clinically. The mechanisms
underlying development of tolerance are not fully understood. Pain signals at the level of the
spinal cord, modulates the release of different neurotransmitters and neuropeptides. Also,
previous studies in our laboratory have shown that co-administration of calcium channel blockers
attenuate morphine tolerance. Neuropeptide Y (NPY) is abundantly expressed in the dorsal horn
of the spinal cord and has been reported to have anti-nociceptive effect. Consequently, the effect
of NPY on morphine-induced tolerance was investigated in rats.

Methods

Male Sprague Dawley rats (275-325g) were implanted with intrathecal catheters
(ReCath Co, USA). These were divided randomly into groups and administered the following
drugs: Saline, Morphine (10µg), NPY (10µg) and NPY+ morphine. Behavioural assessment of
anti-nociception was performed by hot-plate test daily for 9 days. Expression of NPY in the
spinal cord was observed by immunohistochemistry and RT-PCR in morphine treated rats.

Results

Repeated intrathecal administration of morphine produced tolerance in the hot-plate test.
Administration of NPY alone produced an antinociceptive effect which was less than morphine.
However, combined administration of NPY and morphine led to a significantly higher
antinociceptive effect with delayed onset of tolerance. Expression of NPY in the spinal cord not
significantly altered.

Conclusions

Co-administration of NPY persistently enhanced antinociceptive effect with
attenuation of tolerance. However, the expression of NPY was not significantly altered in
tolerant rats in the current study. The mechanism of this effect is being analyzed currently

References

1. Malkmus, S.A., Yaksh, T.L., 2004. Intrathecal catheterization and drug delivery in the
rat. Methods Mol. Med. 99, 109–121.
2.Upadhya, M. A., Dandekar, M. P., Kokare, D. M., Singru, P. S., & Subhedar, N. K. (2009). Involvement of neuropeptide Y in the acute, chronic and withdrawal responses of morphine in nociception in neuropathic rats: behavioral and neuroanatomical correlates. Neuropeptides, 43(4), 303–314.

Presenting Author

Perminder Singh

Poster Authors

PERMINDER SINGH

MSc

All India Institute of Medical Sciences New Delhi

Lead Author

E-mail

Topics

  • Mechanisms: Biological-Systems (Physiology/Anatomy)