Clinical studies have reported lower effectivity of
opioid drugs in
therapy of
neuropathic pain. Therefore, to determine the changes in endogenous
opioid systems in this
pain more precisely, we have studied the changes in the
pain-related behavior on days 1, 14, and 28 following a chronic constriction injury (CCI) to the sciatic nerve in mice. In parallel, we have studied the changes of μ-(MOP), δ-(DOP) and κ-(KOP) receptors,
proenkephalin (PENK) and
prodynorphin (PDYN)
mRNA levels, as well as GTPγS binding of
opioid receptors on the ipsi- and contralateral parts of the spinal cord and thalamus on the 14th day following CCI, as on this day the greatest manifestation of
pain-related behavior was observed. On ipsilateral spinal cord, the decrease in MOP/DOP/KOP receptor and increase in PDYN/PENK
mRNA expression was observed. In thalamus, MOP/DOP/KOP receptor expression decreased contralaterally. On ipsilateral side, there were no changes in PDYN/PENK or DOP/KOP receptor expression, but MOP
mRNA decreased. The spinal GTPγS binding of MOP/DOP/KOP receptor
ligands decreased on the ipsilateral side, yet the effect was less pronounced for DOP receptor
ligands. In thalamus, a decrease was observed on the contralateral side for all
opioid receptor ligands, especially for DOP
ligand. A less pronounced decrease in GTPγS binding of spinal DOP
ligands may indicate a weaker stimulation of ascending nociceptive pathways, which could explain the absence of decreased activity of DOP receptor
ligands in neuropathy. These findings may suggest that drugs with a higher affinity for the DOP receptor will perform better in
neuropathic pain.