Study On The Effects Of Cgrp On The Modulation Of The Primary Sensory Information In Pain

Part 1. The effects of CGRP and CGRP receptor antagonist CGRP_8-37 on paw withdrawal mechanical threshold (PWTL) in capsaicin-induced pain in rats.Objective: In this study, we made the neuropathic pain model through injecting capsaicin around the dorsal thigh sciatic nerve in rats, then gave exogenous CGRP and CGRP receptor antagonist CGRP_8-37 by intraperitoneal injection to explore the effects of CGRP on thermal hyperalgesia in capsaicin-induced pain in rats.Methods: To investigate these effects, 48 SD rats were randomly divided into 6 groups: Group A: normal control group; Group B: saline group; Group C: capsaicin group; Group D: intraperitoneal injection of saline + Capsaicin injection; Group E: intraperitoneal injection of CGRP + Capsaicin injection; Group F: intraperitoneal injection CGRP_8-37 + Capsaicin injection. Each group was done with hot-plate test with the duration of 10,20,30,40,50,60 min before and after experiment.Results:(1) The PWTL of rats were significantly shortened after injection of capsaicin (P<0.05). (2) After CGRP was given in capsaicin-induced pain rats as an intervention, the PWTL of rats were significantly shorter than the single injection of capsaicin (P<0.05). (3) After CGRP_8-37 was given in capsaicin-induced pain rats as an intervention, the PWTL of rats were prolonged than the single injection of capsaicin(P<0.05).Conclusion: According to experimental results, CGRP may play a role in promoting nociceptive pain information in rats and resulting in hyperalgesia by combining its receptors.Part 2. The Expression of CGRP changes in spinal cord and dorsal root ganglion after capsaicin-induced pain in ratsObjective: Our study was to investigate whether CGRP was involved in the modulation of the primary sensory information. With immunohistochemical technique, we observed the expression of CGRP changes in dorsal root ganglion (DRG) and the corresponding segments of spinal cord after capsaicin-induced pain in rats.Methods: To investigate these effects, 40 SD rats were randomly divided into 5 groups, Group A: normal control group; Group B: saline group; Group C: capsaicin 1 h group; Group D: capsaicin 12 h group; Group E: capsaicin 24 h group. Respectively given intraperitoneal anesthesia after 1 h, 12 h, 24 h, 4% para formaldehyde (4℃) was perfused from ascending aorta to left ventricle to fix the sample, then dorsal root ganglia and spinal cord was removed to stripped slices, with immunohistochemistry, microscopy, computer image analysis.Results:(1) In saline group and capsaicin 1 h group, the positive expression rate of CGRP in DRG Neurons in Rats showed no difference (P>0.05), the gray value of CGRP positive neurons increased (P<0.05). Compared capsaicin 12 h group with capsaicin 1 h group, the positive expression rate of CGRP mediated DRG neurons obviously increased (p<0.05), and the gray value decreased (P<0.05). Between capsaicin 24 h group and capsaicin 12 h group, the positive expression rate of CGRP neurons in DRG obviously increased (P<0.05), and the gray value decreased (P<0.05).(2) In saline group and capsaicin 1 h group, the gray value of CGRP positive neurons in the spinal dorsal horn markedly increased (P<0.05). Compared capsaicin 12 h group with capsaicin 1 h group, the gray value of CGRP positive neurons in the spinal dorsal horn obviously decreased (P<0.05). Between capsaicin 24 h group and capsaicin 12 h group, the gray value of CGRP positive neurons in the spinal dorsal horn decreased (P<0.05) in capsaicin 24 h group.(3) In saline group and capsaicin 1 h group, the gray value of CGRP positive neurons in anterior horn of spinal cord increased but no difference (P>0.05). Compared capsaicin 12 h group with capsaicin 1 h group, the gray value of CGRP positive neurons in anterior horn of spinal cord obviously decreased (P<0.05). Between capsaicin 24 h group and capsaicin 12 h group, the gray value of CGRP positive neurons in anterior horn of spinal cord decreased (P<0.05) in capsaicin 24 h group.Conclusion: According to the experimental results, Expression of CGRP is significantly up-regulated after capsaicin-induced pain in DRG and the corresponding segment spinal cord neurons, which indicates that CGRP is involved in the modulation of nociceptive pain information transmission on the level of spinal cord.