Opioids have a selective effect on nociception with little effect on other sensory modalities. However, the cellular mechanisms for this preferential effect are not fully known. Two broad classes of nociceptors can be distinguished based on their growth factor requirements and binding to isolectin B4 (IB4). In this study, we determined the difference in the modulation of voltage-gated Ca2+ currents by [D-Ala 2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO, a specific μ oploid agonist) between IB4-positive and -negative small dorsal root ganglion (DRG) neurons. Whole-cell voltage-clamp recordings were performed in acutely isolated DRG neurons in adult rats. Both 1-10 μM DAMGO and 1 to 10 μM morphine had a greater effect on high voltage-activated Ca2+ currents in IB4-negative than IB4-positive cells. However, DAMGO had no significant effect on T-type Ca2+ currents in both groups. The N-type Ca2+ current was the major subtype of Ca 2+ currents inhibited by DAMGO in both IB4-positive and -negative neurons. Although DAMGO had no effect on L-type and R-type Ca 2+ currents in both groups, it produced a larger inhibition on N-type and P/Q-type Ca2+ currents in IB4-negative than IB 4-positive neurons. Furthermore, double labeling revealed that there was a significantly higher μ opioid receptor immunoreactivity in IB 4-negative than IB4-positive cells. Thus, these data suggest that N-and P/Q-type Ca2+ currents are more sensitive to inhibition by the μ opioids in IB4-negative than IB 4-positive DRG neurons. The differential sensitivity of voltage-gated Ca2+ channels to the μ opioids in subsets of DRG neurons may constitute an important analgesic mechanism of μ opioids.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Dec 2004|
ASJC Scopus subject areas
- Molecular Medicine