Evolution of mirror-image pain in temporomandibular joint osteoarthritis mouse model

Abstract Mirror-image pain is a kind of pain that occurs on the contralateral side, but its pathogenesis remains unclear. Objective To develop an osteoarthritis mouse model for investigating mirror-image pain through observing nocifensive behaviors, histological changes, and nociceptive activity at days 3, 7, 14, 21, and 28 after the chemical induction of unilateral temporomandibular joint (TMJ) osteoarthritis. Methodology We randomly divided 6-week-old mice into sham and complete Freund adjuvant groups. To induce nocifensive behaviors, we applied 0.04 g of von Frey filament, 10 psi of air puff, and cold acetone on both sides of whisker pads at different days. The histology of TMJ on both sides was observed by hematoxylin/eosin staining and microcomputed tomography scanning. Furthermore, the nociceptive activity was evaluated using the phosphorylated cyclic AMP response element binding protein (pCREB) and a microglia marker at different days in the trigeminal subnucleus caudalis. Results Nocifensive behaviors against mechanical and temperature stimuli on the contralateral side became stronger than the baseline on day 28, in agreement with the elevation of the pCREB and the microglia marker in the trigeminal subnucleus caudalis. Thus, hypernociception on the contralateral side occurred at day 28. Conclusions Clearly, the TMJ model with unilateral osteoarthritis exhibited mirror-image pain. Therefore, this model is useful in investigating the pathogenesis of pain and in developing treatments.

Analgesic effect and central mechanisms of CQ prescription on cancer invasion induced mirror image pain in model mice / 中国中药杂志

This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain (CIIMIP)in model mice.In the study, male BALB/c mice were randomly divided into normal group, operation control group (injected with 0.2 mL inactivated S180 sarcoma cell sap), model group (injected with 0.2 mL S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and CQ prescription low dose group (intraperitoneally injected with CQ prescription 100 mg•kg⁻¹ on the basis of model mice), CQ prescription middle dose group (intraperitoneally injected with CQ prescription 150 mg•kg⁻¹ on the basis of model mice), and CQ prescription high dose group (intraperitoneally injected with CQ prescription 200 mg•kg⁻¹ on the basis of model mice). Mechanical withdraw threshold (MWT) of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate (Glu), gamma aminobutyric acid (GABA), glycine (Gly), and taurine (Tau) in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector (HPLC-FLD); AimPlex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP-3) in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist (Bicuculline) on analgesic effect of CQ prescription.The results indicated that CQ prescription could remarkably increase MWT of model mice(P<0.01, P<0.05), decrease the level of Glu(P<0.01, P<0.05), improve the levels of GABA, Gly, Tau(P<0.01, P<0.05), lower the ratio of Glu/GABA(P<0.01, P<0.05), and reduce the levels of RANTES, MCP-3(P<0.05) in the L3-L5 spinal cord, and GABAa receptor antagonist significantly blocked the analgesic effect of CQ prescription at two time points(P<0.05).This study showed that CQ prescription had significant analgesic effect on CIIMIP model mice, and its mechanism was associated with regulating the balance between excitability amino acid(EAA) and inhibitory amino acid (IAA) transmitters in central nervous system, partially activating GABAa receptor, and reducing the release of RANTES and MCP-3 in the spinal cord.

Roles of neurochemicals in central nerve system of mirror image pain in cancer invasion pain model and effects of gabapentin on them / 中国生化药物杂志

Objective To study the roles of neurochemicals as Glu, GABA in the spinal cord and SP, DynA1-13 in the cerebral cortex of mirror image pain in cancer invasion pain model and the effects of gabapentin on them.Methods Male BALB/c mices were randomly divided into native group, sham group (injected inactivated S180 sarcoma cell sap), model group (injected 0.2 mL of S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and GBP group (intraperitoneally injected gabapentin 120 mg/kg on the basis of model mice).Mechanical withdraw threshold of the ipsilateral and contralateral hind paw were evaluated by Von Frey hairs before and after surgery.The levels of Glu and GABA in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector ( HPLC-FLD ) and radioimmunoassay was used to detect the concentrations of SP and DynA1-13 in the cerebral cortex.Results The mechanical withdraw threshold of contralateral mirror sites in model mice appeared same trend and approximate degree of decline, following the generation of cancer invasion pain of ipsilateral hind paw.Compared with native group, the concentrations of Glu in the spinal cord and SP in the cerebral cortex in model group were significantly increased (P<0.05, P<0.01), and the levels of GABA in the spinal cord and Dyn A1-13 in the cerebral cortex in model group were significantly decreased (P<0.05, P<0.01).Gabapentin could significantly increase the bilateral mechanical withdraw threshold of model mice and the analgesic effect could maintain to 240 min after administration (P<0.05 or P<0.01).Moreover, gabapentin could reverse the changes of above neurochemicals in the central nervous system of mirror image pain in cancer invasion pain model mice (P<0.01 or P<0.05).Conclusion The mirror image pain phenomenon does exist in the cancer invasion pain model mice induced by S180 sarcoma.The mechanism of mirror image pain occurr and preserve in cancer invasion pain model may involve the changes of Glu, GABA in the spinal cord and SP, Dyn A1-13 in the cerebral cortex, through which gabapentin can relieve mirror image pain in cancer invasion pain model.

Effect of preemptive local injection of ropivocaine with dexmedetomidine on mirror pain in rats and its mechanism

OBJECTIVE@#To observe the effect of preemptive local injection of ropivocaine with dexmedetomidine on activation of glial cells and on the mirror pain in rats and its mechanism.@*METHODS@#A total of 48 adult male Sprague-Dawley rats (weighing 180 g-220 g) were included in the study and randomized into 3 groups, Group S, Group R, and Group RD1. A rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established in the three groups. Before procedures and nerve extraction, Group S (n = 16) was injected 0.9% saline locally; Group R (n = 16) was injected 0.5% ropivocaine locally, and Group RD1 (n = 16) was injected 0.5% ropivocaine in combined with 1 μg dexmedetomidine locally. After the model being established in the three groups, 8 rats were used for behavior test until 28 d, and dorsal root ganglions (DRGs) of the other 8 rats were harvested on the 3rd day after surgery. Immunofluorescent and transmission electron microscopy were used to observe the activation of glial cells in DRG, and the behavior test results in the three groups were compared.@*RESULTS@#The results showed that mechanical pain threshold in ipsilateral hind-paws of the Group S, Group R, Group RD1 animals dropped to (3.640 ± 1.963) g, (5.827 ± 1.204) g, (7.482) ± 1.412 g at 3 d respectively; while in contralateral paws dropped to (7.100 ± 1.789) g, (17.687 ± 1.112) g, (16.213 ± 1.345) g on the 3 d respectively. Immunofluorescent showed that the glial cells were activated in bilateral side DRG after surgery in 3 groups, but ipsilateral paws expressed more active glial cells than contralateral paws. Transmission electron microscopy showed that mitochondria swelling/vacuolization and lysosomes were more obvious in ipsilateral paws than contralateral paws, but Group RD1 formula could reduce glial cells activity, mitochondria swelling/vacuolization and the amount of lysosomes.@*CONCLUSIONS@#Local injection of ropivocaine and/or dexmedetomidine can effectively inhibit the activation of glial cells in DRG, mitigate the pathological changes of neuron in DRG and reduce mirror image pain.

Effect of preemptive local injection of ropivocaine with dexmedetomidine on mirror pain in rats and its mechanism

Objective: To observe the effect of preemptive local injection of ropivocaine with dexmedetomidine on activation of glial cells and on the mirror pain in rats and its mechanism. Methods: A total of 48 adult male Sprague-Dawley rats (weighing 180 g-220 g) were included in the study and randomized into 3 groups, Group S, Group R, and Group RD

INVOLVEMENT OF SPINAL ENDOMORPHIN 2 IN MIRROR-IMAGE PAIN INDUCED BY PERIPHERAL INFLAMMATION / 神经解剖学杂志

The present investigation was designed to study, whether endogenous antinociceptive system is effective on mirror-image pain induced by peripheral inflammation. After Complete Freund's adjuvant (CFA) was subcutaneously injected into one hindpaw, besides heat hyperalgesia and mechanical allodynia from 1 h to 72 h at the injured site, contralateral mechanical allodynia was also induced at 1 h and significantly lasted for 24 h after injection, which was called mirror-image pain. To explore the effects of endogenous antinociceptive system on mirror-image pain, endomorphin (EM) 2 was intrathecally administered at doses of 0.2 μg, 2 μg, 20 μg and EM1 was given at the maximum dose of 20 μg by the same way, respectively, 10 min prior to CFA injection. The present results showed that three doses of EM2could reverse the decreased contralateral mechanical threshold from 48.03 ± 9.07 mN ( pre-treatment with vehicle) to 200.49 ± 53.68mN, 247.63 ± 49.43 mN and 250.57 ± 55.34 mN ( pre-treatments with EM2 ), respectively, but not in a significantly dose-dependent manner. On the other hand, intrathecal pre-treatment with EM1, the contralateral mechanical threshold was 51.24 ± 12.59 mN after CFA injection, which was similar to that pre-treatment with vehicle. It indicates that spinal EM1 did not have remarkable effect on mirror-image pain behavior. The present results provide evidence for that spinal EM2, but not EM1, mainly originated from the endogenous antinociceptive system might play an inhibitory role in mirror-image mechanical allodynia induced by peripheral tissue inflammation.