Abstract
BackgroundNeuropathic pain is a chronic and intractable symptom associated with nerve injury. The periaqueductal gray (PAG) is important in the endogenous pain control system and is the main site of the opioidergic analgesia. To investigate whether neuropathic pain affects the endogenous pain control system, we examined the effect of neuropathic pain induced by sacral nerve transection on presynaptic GABA release, the kinetics of postsynaptic GABA-activated Cl- currents, and the modulatory effect of μ-opioid receptor (MOR) activation in mechanically isolated PAG neurons with functioning synaptic boutons.ResultsIn normal rats, MOR activation inhibited the frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) to 81.3% of the control without any alteration in their amplitude. In neuropathic rats, the inhibition of mIPSC frequency by MOR activation was 82.4%. The frequency of GABAergic mIPSCs in neuropathic rats was 151.8% of normal rats without any difference in the mIPSC amplitude. Analysis of mIPSC kinetics showed that the fast decay time constant and synaptic charge transfer of mIPSCs in neuropathic rats were 76.0% and 73.2% of normal rats, respectively.ConclusionsThese results indicate that although the inhibitory effect of MOR activation on presynaptic GABA release is similar in both neuropathic and normal rats, neuropathic pain may inhibit endogenous analgesia in the PAG through an increase in presynaptic GABA release.
Highlights
Neuropathic pain is a chronic and intractable symptom associated with nerve injury
GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in periaqueductal gray (PAG) neurons isolated from neuropathic rats There were no differences in morphological characteristics between normal and neuropathic rats
We recorded and measured the mean amplitude and frequency of mIPSCs 20 min after the rupture of the patch membrane because it took 10-20 min for synaptic currents to stabilize (Figure 1). Recordings of these mIPSCs were stable for approximately 60 min, which indicated that the presynaptic nerve terminals attached to the dissociated PAG neurons were functional and that their spontaneous activity was stable for at least 60 min
Summary
The periaqueductal gray (PAG) is important in the endogenous pain control system and is the main site of the opioidergic analgesia. To investigate whether neuropathic pain affects the endogenous pain control system, we examined the effect of neuropathic pain induced by sacral nerve transection on presynaptic GABA release, the kinetics of postsynaptic GABA-activated Cl- currents, and the modulatory effect of μ-opioid receptor (MOR) activation in mechanically isolated PAG neurons with functioning synaptic boutons. Several studies have shown that administration of morphine or opioid peptides, either systemically or directly into the PAG, produces antinociception, which is thought to be associated with inhibition of neuronal activity in the PAG [20,21]. We have shown that MOR activation inhibits presynaptic GABA release in acutely isolated PAG neurons from normal young rats [26]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
