Role of the phosphatidylinositol-specific phospholipase C pathway in δ-opioid receptor-mediated antinociception in the mouse spinal cord
Section snippets
Animals
Male Institute of Cancer Research mice weighing 23–27 g (SASCO, Omaha, NE, USA) were used. All experiments were approved by and conformed to the guidelines of the Medical College of Wisconsin Animal Care Committee. Every effort was made to minimize the numbers and any suffering of animals used in the following experiments. Animals were housed five per cage in a room maintained at 22±0.5°C with an alternating 12-h light–dark cycle. Food and water were available ad libitum. Animals were used only
Effects of intrathecal pretreatment with the phospholipase C inhibitors, neomycin, U73122 and ET-18-OCH3, on antinociception induced by intrathecal administration of [d-Ala2]deltorphin II
The experiments were designed to determine whether PLC could be involved in [d-Ala2]deltorphin II-induced antinociception in the spinal cord. Neomycin and U73122 are selective inhibitors of PLC.20., 38. ET-18-OCH3 is a selective inhibitor of phosphatidylinositol (PI)-specific PLC.27 Groups of mice were pretreated intrathecally with saline, neomycin (5.5, 11.0 or 22.0 nmol; 5, 10 or 20 μg), vehicle (50% DMSO in 0.9% NaCl), U73122 (2.7, 4.0 or 5.4 nmol; 1.25, 1.88 or 2.50 μg) or ET-18-OCH3 (0.095,
Discussion
Recent work with cell lines has demonstrated that some δ-opioid receptors may be linked to the PLC pathway. In the mouse periaqueductal gray matter and spinal cord, δ-opioid receptor agonists, such as [d-Ala2]deltorphin II and [d-Pen2,5]enkephalin, cause an increase in inositol phosphate accumulation.23., 25. These findings support the idea that the PLC pathway may, at least in part, contribute to the antinociception induced by δ-opioid receptor agonists.
Several PLC inhibitors are currently
Conclusions
The present study reveals a potential role for the PLC–IP3 pathway in the expression of antinociceptive responses regulated by spinal δ-opioid receptors in the mouse. Furthermore, it is most likely that concomitant activation of PKC by δ-opioids results in an autoinhibitory feedback action on the spinal δ-opioid receptor system to produce antinociception.
Acknowledgements
We thank Ms Michiko Narita for technical assistance. This work was mainly supported by US Public Health Service Grant DA 03811 from the National Institute on Drug Abuse, National Institutes of Health.
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2015, NeuroscienceCitation Excerpt :Importantly, intrathecal injection of low-dose U73122, which by itself did not significantly affect animal pain behavior, blocked JHU58-induced inhibition of mechanical hypersensitivity in rats after nerve injury. A previous study showed that intrathecal injection of low-dose U73122 also attenuated the analgesia induced by intrathecal injection of a delta-opioid receptor agonist (Narita et al., 2000). Our findings suggest that the pain inhibition by intrathecal JHU58 is dependent on activation of the PLC pathway.
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2013, Life SciencesCitation Excerpt :Previous work has demonstrated that CaCCs are, at least in part, involved in the production of the δ-opioid receptor-mediated antinociception in the mouse spinal cord (Yamazaki et al., 2000). This finding indicates that the release of Ca2 + from the IP3-sensitive Ca2 + pool due to δ-opioid receptor stimulation may lead to the opening of Ca2 +-activated ion channels, CaCCs and Ca2 +-activated K+ channels, resulting in neuron hyperpolarization (Narita et al., 2000). Recently, our group demonstrated for the first time that the peripheral and central antinociceptive effects of the δ opioid receptor agonist SNC80 were inhibited, at least in part, by the CaCC blocker niflumic acid (Pacheco et al., 2012a, 2012b).
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