Chen C-C1,2, Shih Y-C1, Huang C-W3, Liu Y-L1
1Chang Gung University, Department of Physical Therapy, Taoyuan, Taiwan, 2Chang-Gung Memorial Hospital, Department of Physical Medicine and Rehabilitation, Taoyuan, Taiwan, 3University of Fo Guang, Department of Psychology, Yilan, Taiwan
Background: Insular cortex was one of the important relay stations which involved the looping of the central thermal disinhibition pathway to modulate the antalgic effects on central post-stroke pain. The effects were supposed to be activated by the opioid receptors on the cortex. However, it is little known about the kinds of opioid receptors involved. the selectivity of antagonist was used to examine the receptors on the insular cortex in the rat with induced thalamic damage. It is a common animal model of central post-stroke pain.
Purpose: This study aims to examine the mu-opioid receptor on the insular cortex in the rat model with thalamic damage using the antagonist and agonist of opioid receptors.
Methods: Adult male Sprague-Dawley rats (250-300g) were induced the CPSP by the injection of type IV collagenase (0.025 µl/0.05 U; Sigma) under stereotaxic guidance to damage right ventral posterolateral nucleus of the thalamus under anesthesia. After a week rest, the cannula was implanted into rostal agranular insular cortex (RAIC) with microdialysis fibers under anesthesia. On one week more, the mu-opioid receptor agonist DAMGO (0.2mM; Sigma) was infused into right RAIC area under anesthesia. Once the opioid antagonists were microinjected for five minutes, the antagonists were applied including naloxone hydrochloride (mu-opioid receptor antagonist; 1mM/10mM/20mM; Sigma; n=6/dosage), naltrinodole hydrochloride (delta-opioid receptor antagonist; 0.1mM/1mM/2mM; Merk, n=7/dosage), or nor-BNI (kappa-opioid receptor antagonist, 1mM/2mM/4mM; Tocris Cookson; n=7/dosage). The paw withdrawal latency (PWL) to radiant heat (Plantar Test Apparatus Model 435; IITC, USA) was measured before (baseline) and after the infusion of DAMGO, and then after the antagonists were applied.
Results: The agonist DAMGO significantly increased the PWL on left hind paw compared to the base (10.39±1.07 vs. 19.59±2.63 seconds, p 0.05, Wilcoxon test, SPSS 19). The antagonist 20mM naloxone significantly reversed the elevated PWL on left hind paw, activated by the DAMGO (9.23±2.51 vs. 19.59±2.63 seconds, p 0.05, Wilcoxon test, SPSS 19) when the other antagonists with dosages did not.
Conclusion(s): The naloxone, but not other antagonists, reversed the antalgic effect activated by mu-opioid receptor agonist DAMGO on the insular cortex in the rats with induced thalamic damage.
Implications: The findings may suggest one of the underlying mechanism of the antalgic effect on central post-stroke pain once physical modalities is used.
Keywords: Central post-stroke pain, opioid receptor, insular cortex
Funding acknowledgements: The present work was supported by Chang-Gung University (EMRPD1H0391), Chang-Gung Memorial Hospital (CMRPD1F0071), Ministry of Science and Technology (MOST 107-2314-B-182-022)
Purpose: This study aims to examine the mu-opioid receptor on the insular cortex in the rat model with thalamic damage using the antagonist and agonist of opioid receptors.
Methods: Adult male Sprague-Dawley rats (250-300g) were induced the CPSP by the injection of type IV collagenase (0.025 µl/0.05 U; Sigma) under stereotaxic guidance to damage right ventral posterolateral nucleus of the thalamus under anesthesia. After a week rest, the cannula was implanted into rostal agranular insular cortex (RAIC) with microdialysis fibers under anesthesia. On one week more, the mu-opioid receptor agonist DAMGO (0.2mM; Sigma) was infused into right RAIC area under anesthesia. Once the opioid antagonists were microinjected for five minutes, the antagonists were applied including naloxone hydrochloride (mu-opioid receptor antagonist; 1mM/10mM/20mM; Sigma; n=6/dosage), naltrinodole hydrochloride (delta-opioid receptor antagonist; 0.1mM/1mM/2mM; Merk, n=7/dosage), or nor-BNI (kappa-opioid receptor antagonist, 1mM/2mM/4mM; Tocris Cookson; n=7/dosage). The paw withdrawal latency (PWL) to radiant heat (Plantar Test Apparatus Model 435; IITC, USA) was measured before (baseline) and after the infusion of DAMGO, and then after the antagonists were applied.
Results: The agonist DAMGO significantly increased the PWL on left hind paw compared to the base (10.39±1.07 vs. 19.59±2.63 seconds, p 0.05, Wilcoxon test, SPSS 19). The antagonist 20mM naloxone significantly reversed the elevated PWL on left hind paw, activated by the DAMGO (9.23±2.51 vs. 19.59±2.63 seconds, p 0.05, Wilcoxon test, SPSS 19) when the other antagonists with dosages did not.
Conclusion(s): The naloxone, but not other antagonists, reversed the antalgic effect activated by mu-opioid receptor agonist DAMGO on the insular cortex in the rats with induced thalamic damage.
Implications: The findings may suggest one of the underlying mechanism of the antalgic effect on central post-stroke pain once physical modalities is used.
Keywords: Central post-stroke pain, opioid receptor, insular cortex
Funding acknowledgements: The present work was supported by Chang-Gung University (EMRPD1H0391), Chang-Gung Memorial Hospital (CMRPD1F0071), Ministry of Science and Technology (MOST 107-2314-B-182-022)
Topic: Pain & pain management
Ethics approval required: Yes
Institution: Chang Gung University
Ethics committee: Institutional Animal Care and Use Committee
Ethics number: IACUC Approval No.: CGU 11-044
All authors, affiliations and abstracts have been published as submitted.
