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Spinal cord ischemia reduces mu-opioid receptors in rats: correlation with morphine insensitivity
1Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.
Abstract:
The present study examined the effects of spinal cord ischemia on the expression of mu-opioid receptors in rat dorsal spinal cord and the effects of intrathecal (i.t.) morphine on the acute mechanical allodynia that developed after spinal ischemia. The mechanical allodynia was not significantly alleviated by up to 10 microg i.t. morphine, a dose which caused strong antinociception in the tail flick test. Immunohistochemical staining demonstrated that the level of mu-opioid receptor expression in the dorsal horn of spinal cord segments receiving input from the allodynic skin was markedly reduced 2 days after ischemia, when the rats were allodynic. The results indicate that spinal cord ischemia reduces the expression of mu-opioid receptors in rat dorsal horn, which may be one of the underlying mechanisms of morphine insensitivity for treating acute allodynia after spinal ischemia.
Insights
Spinal cord ischemia reduces mu-opioid receptors in rats, leading to morphine insensitivity for acute pain. This study reveals a potential mechanism for treatment resistance after spinal cord injury.
Area of Science:
- Neuroscience
- Pain Research
- Spinal Cord Injury
Background:
- Spinal cord ischemia can cause persistent neuropathic pain.
- Opioid analgesics are commonly used for pain management.
- The role of mu-opioid receptors in post-ischemic pain is not fully understood.
Purpose of the Study:
- To investigate the impact of spinal cord ischemia on mu-opioid receptor expression.
- To evaluate the efficacy of intrathecal morphine in treating mechanical allodynia post-ischemia.
Main Methods:
- Rats underwent spinal cord ischemia.
- Mechanical allodynia was assessed.
- Intrathecal morphine was administered.
- Immunohistochemical staining quantified mu-opioid receptor levels in the dorsal spinal cord.
Main Results:
- Intrathecal morphine did not alleviate mechanical allodynia post-ischemia.
- Mu-opioid receptor expression in the dorsal horn was significantly reduced 2 days after ischemia.
- Reduced receptor levels correlated with the presence of allodynia.
Conclusions:
- Spinal cord ischemia decreases mu-opioid receptor expression in the rat dorsal horn.
- This reduction may explain the lack of pain relief from morphine in acute allodynia following spinal ischemia.
- Findings suggest novel therapeutic targets for managing post-ischemic neuropathic pain.