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Changes of opioid binding density in the rat spinal cord following unilateral dorsal rhizotomy
1Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis, USA.
Abstract:
Mu, delta and kappa opioid receptors in the vertebrate spinal cord mediate the potent antinociceptive effects of opioid agonists administered onto the spinal cord. The present experiments were conducted to determine the effect of unilateral dorsal rhizotomy on mu, delta and kappa spinal opioid binding sites. Measurements of opioid binding were made at 1, 2, 4 or 8 days after rhizotomy and comparisons were made to intact animals. The changes in mu, delta and kappa opioid binding sites were determined by receptor autoradiography using the highly selective radioligands [3H]sufentanil, [3H]DPDPE and [3H]U69593, respectively. Within autoradiograms of each spinal cord, three regions on each side of the spinal cord were targeted for densitometric analysis: laminae I-II (medial), V (lateral) and X. When effects of unilateral rhizotomy within animals were assessed by comparison of the density of binding on the side ipsilateral to the rhizotomy to the contralateral side, decreases in the binding of all three radioligands were observed in laminae I-II on the side of the spinal cord ipsilateral to the rhizotomy at 2-8 days postlesion. A significant reduction in binding was also noted for mu and delta sites in lamina V after 8 days and for delta binding in lamina X at 2 and 4 days on the side ipsilateral to the rhizotomy. However, when densities of binding sites were compared with the corresponding regions in control, it was clear that dorsal rhizotomy resulted in significant changes in opioid binding on both sides of the spinal cord; changes differed for each type of opioid binding site. On the contralateral side of the spinal cord, rhizotomy caused a significant decrease of mu opioid sites 1 day after the lesion and showed partial recovery by day 8. Delta opioid sites were also significantly decreased as early as 1 day postlesion, but did not recover. Kappa opioid sites did not change at 1 day after the rhizotomy but increased on day 2, decreased on day 4 and fully recovered 8 days after rhizotomy. The present results support the hypothesis that a significant proportion of spinal mu, delta and kappa opioid binding sites are present on the central terminations of primary afferents. Finally the present data are the first to report a contralateral effect of the unilateral rhizotomy on spinal opioid binding sites. The contralateral changes in binding were specific to the type of opioid site examined, time after the surgery and region of the spinal cord examined.
Insights
Unilateral dorsal rhizotomy significantly alters spinal opioid binding sites, affecting both sides of the spinal cord. These changes in mu, delta, and kappa opioid receptors indicate their presence on primary afferent terminals.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Spinal mu, delta, and kappa opioid receptors are crucial for antinociception.
- Opioid agonists administered spinally exert potent pain-relieving effects.
- The precise localization of these receptors within the spinal cord is not fully understood.
Purpose of the Study:
- To investigate the impact of unilateral dorsal rhizotomy on spinal mu, delta, and kappa opioid binding sites.
- To determine the time course and regional distribution of these changes.
- To assess whether these binding sites are located on primary afferent neurons.
Main Methods:
- Unilateral dorsal rhizotomy was performed on vertebrate spinal cords.
- Opioid binding site densities were measured using receptor autoradiography at 1, 2, 4, and 8 days post-lesion.
- Selective radioligands ([3H]sufentanil, [3H]DPDPE, [3H]U69593) were used for mu, delta, and kappa receptors, respectively.
- Densitometric analysis was performed in laminae I-II, V, and X on both ipsilateral and contralateral sides.
Main Results:
- Unilateral rhizotomy decreased mu, delta, and kappa opioid binding in the ipsilateral laminae I-II (2-8 days post-lesion).
- Significant reductions in mu and delta binding were observed in lamina V (8 days) and delta binding in lamina X (2-4 days) ipsilaterally.
- Contralateral effects included decreased mu binding (1 day, partial recovery by 8 days), persistent delta binding decrease, and transient kappa binding changes (increase at 2 days, decrease at 4 days, recovery by 8 days).
Conclusions:
- A substantial portion of spinal mu, delta, and kappa opioid binding sites are located on the central terminals of primary afferents.
- Unilateral dorsal rhizotomy induces significant, time-dependent, and region-specific changes in opioid binding on both sides of the spinal cord.
- This study provides the first evidence of contralateral effects of unilateral rhizotomy on spinal opioid binding sites.
