Antisense oligonucleotide knockdown of mGlu5 receptor attenuates the antinociceptive tolerance and up-regulated expression of spinal protein kinase C associated with chronic morphine treatment

Effect of metabotropic glutamate 5 receptor antagonists on morphine efficacy and tolerance in rats with neuropathic pain

“…This is an expansion from our previous studies (Liu et al, 2009;Xu et al, 2008Xu et al, , 2012) of naïve animal model to a neuropathic pain model. The results are consistent with each other.…”

“…The interaction between mGlu 5 receptor antagonists and morphine in terms of antinociception effects and morphine tolerance has been researched extensively in naïve rats (Narita et al, 2005;Smith et al, 2004;Xu et al, 2007Xu et al, , 2012, but rarely in rats with chronic pain, and there has been great variation in the results. In a chronic neuropathic pain model, systemically administered MPEP potentiated morphine's antiallodynia effect and attenuated morphine tolerance if used preemptively (Osikowicz et al, 2008).…”

Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance

“…(2) Cellular adaptations, which include gene expression [113][114][115] and the reduction in MOR function. An exemplar study of the latter is that increased activity of NMDAR by PKC/PKA-induced phosphorylation of its GluN2A and GluN2B subunits leads to higher calcium influx, increased release of NO, and subsequent negative regulation of MOR activity [116].…”

“…Pharmacological studies have identified several signaling proteins involved in the interaction between glutamate/NMDAR and opioid/MOR tolerance. Some of them include nitric oxide synthase (NOS), protein kinase C (PKC), protein kinase A (PKA), calcium (Ca 2+ )/calmodulin (CaM)-dependent kinase II (CaMKII), delta-opioid receptor (DOR) and the regulators of G-protein signaling (RGS) proteins [114,117,118].…”