Expression of opioid receptor-like 1 (ORL1) & mu opioid receptors in the spinal cord of morphine tolerant mice.
OBJECTIVE
The mechanism underlying the development of tolerance to morphine is not clearly understood though a number of factors have been implicated. One of the likely factors may be increased activity of anti-opioid peptides like nociceptin (also known as orphanin FQ or N/OFQ). N/OFQ and morphine bind to opioid receptor-like 1 (ORL1) receptor and muopioid receptor respectively. The present work was undertaken to investigate the density of ORL1 and mu (mu) receptor expression in the spinal cord of mice after inducing morphine tolerance.


METHODS
Swiss albino mice were injected with either morphine (experimental group, n=15) or saline (control, n=15), twice a day for 9 days. The development of tolerance was noted by the hotplate test. Cryostat sections of the cervical region of spinal cord were labeled with specific ligands to localize ORL1 and mu receptors. The density of receptor expression over laminae I-II of spinal cord was evaluated using image analysis system.


RESULTS
The morphine treated mice developed tolerance by day 9 as evident by the hot plate test. Both receptors were selectively expressed at a higher concentration over the superficial laminae (I-II) of the dorsal horn, indicating a role in pain processing. An increased expression of ORL1 receptors was also noted over the gray matter around the central canal. Quantitative analysis showed an increased expression of ORL1 and mu receptors though the increase was not statistically significant.


CONCLUSIONS
The present study showed that both, ORL1 and mu-opioid receptors were expressed in areas of the spinal cord, concerned with transmission of pain signals. The density of these receptors increased in the superficial laminae (I-II) though not significantly from control after morphine tolerance. The increase in ORL1 receptors could oppose the analgesic action of morphine, contributing to tolerance. Further studies need to be done to elucidate the mechanism of morphine tolerance.
Ray
S B
SB
Department of Anatomy, All India Institute of Medical Sciences, New Delhi , India. sbr_aiims@hotmail.com
Gupta
Y K
YK
Wadhwa
Shashi
S
D000818:Animals; D001345:Autoradiography; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D000094942:Nociceptin Receptor
D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse