Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats
Abstract Background More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral ne...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-09-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-017-0960-0 |
| _version_ | 1818266418891718656 |
|---|---|
| author | Juan Niu Dujuan Huang Rui Zhou MingXia Yue Tao Xu Junna Yang Li He Hong Tian XiaoHong Liu Junwei Zeng |
| author_facet | Juan Niu Dujuan Huang Rui Zhou MingXia Yue Tao Xu Junna Yang Li He Hong Tian XiaoHong Liu Junwei Zeng |
| author_sort | Juan Niu |
| collection | DOAJ |
| description | Abstract Background More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. Methods Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain. The paw withdrawal latency (PWL) was used to evaluate thermal hyperalgesia in neuropathic rats. The expression of P2Y12 and P2Y13 receptors, p-p38MAPK, and NF-kappaBp65 was detected with RT-PCR and western blotting analysis. Results Treatment with AM1241 produces a pronounced inhibition of CCI-induced thermal hyperalgesia and significantly inhibited the increased expression of P2Y12 and P2Y13 receptors at the mRNA and protein levels, which open up the possibility that P2Y12 and P2Y13 receptor expression are downregulated by CB2 receptor agonist AM1241 in CCI rats. Western blot analysis demonstrated that AM1241 reduced the elevated expression of p-p38MAPK and NF-κBp65 in the dorsal spinal cord induced by CCI. After administration with either SB203580 (p38MAPK inhibitor) or PDTC (NF-kappaB inhibitor), the levels of P2Y13 receptor expression in the dorsal spinal cord were lower than those in the CCI group. However, in CCI rats, the increased expression of P2Y12 receptor was prevented by intrathecal administration of PDTC but not by SB203580. In addition, minocycline significantly decreased the increased expression of P2Y12 and P2Y13 receptors. The similar results can be observed in ADPbetaS-treated rats. Intrathecal injection of ADPbataS causes thermal hyperalgesia and increased expression of P2Y12 and P2Y13 receptors in the dorsal spinal cord of naive rats. Moreover, intrathecal injection of AM1241 alleviates pain response and reduces the elevated expression of P2Y12 and P2Y13 receptors, p-p38MAPK, and NF-κBp65 in the dorsal spinal cord of ADPbetaS-treated rats. Intrathecal injection of SB203580 significantly inhibited the ADPbetaS-induced P2Y13 receptor expression, without affecting P2Y12 receptor expression. However, treatment with either SB203580 or PDTC effectively inhibited P2Y13 receptor expression compared to ADPbetaS-treated rats. Conclusions In CCI- and ADPbetaS-treated rats, AM1241 pretreatment could efficiently activate CB2 receptor, while inhibiting p38MAPK and NF-kappaB activation in the dorsal spinal cord. CB2 receptor stimulation decreased P2Y13 receptor expression via p38MAPK/NF-kappaB signaling. On the other hand, CB2 receptor activation decreased P2Y12 receptor expression via p38MAPK-independent NF-kappaB signaling pathway. |
| first_indexed | 2024-12-12T20:06:24Z |
| format | Article |
| id | doaj.art-8e527eaf635c47e787cce353466bbacb |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-12T20:06:24Z |
| publishDate | 2017-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-8e527eaf635c47e787cce353466bbacb2022-12-22T00:13:37ZengBMCJournal of Neuroinflammation1742-20942017-09-0114111210.1186/s12974-017-0960-0Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain ratsJuan Niu0Dujuan Huang1Rui Zhou2MingXia Yue3Tao Xu4Junna Yang5Li He6Hong Tian7XiaoHong Liu8Junwei Zeng9Department of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeDepartment of Physiology, Zunyi Medical CollegeAbstract Background More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. Methods Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain. The paw withdrawal latency (PWL) was used to evaluate thermal hyperalgesia in neuropathic rats. The expression of P2Y12 and P2Y13 receptors, p-p38MAPK, and NF-kappaBp65 was detected with RT-PCR and western blotting analysis. Results Treatment with AM1241 produces a pronounced inhibition of CCI-induced thermal hyperalgesia and significantly inhibited the increased expression of P2Y12 and P2Y13 receptors at the mRNA and protein levels, which open up the possibility that P2Y12 and P2Y13 receptor expression are downregulated by CB2 receptor agonist AM1241 in CCI rats. Western blot analysis demonstrated that AM1241 reduced the elevated expression of p-p38MAPK and NF-κBp65 in the dorsal spinal cord induced by CCI. After administration with either SB203580 (p38MAPK inhibitor) or PDTC (NF-kappaB inhibitor), the levels of P2Y13 receptor expression in the dorsal spinal cord were lower than those in the CCI group. However, in CCI rats, the increased expression of P2Y12 receptor was prevented by intrathecal administration of PDTC but not by SB203580. In addition, minocycline significantly decreased the increased expression of P2Y12 and P2Y13 receptors. The similar results can be observed in ADPbetaS-treated rats. Intrathecal injection of ADPbataS causes thermal hyperalgesia and increased expression of P2Y12 and P2Y13 receptors in the dorsal spinal cord of naive rats. Moreover, intrathecal injection of AM1241 alleviates pain response and reduces the elevated expression of P2Y12 and P2Y13 receptors, p-p38MAPK, and NF-κBp65 in the dorsal spinal cord of ADPbetaS-treated rats. Intrathecal injection of SB203580 significantly inhibited the ADPbetaS-induced P2Y13 receptor expression, without affecting P2Y12 receptor expression. However, treatment with either SB203580 or PDTC effectively inhibited P2Y13 receptor expression compared to ADPbetaS-treated rats. Conclusions In CCI- and ADPbetaS-treated rats, AM1241 pretreatment could efficiently activate CB2 receptor, while inhibiting p38MAPK and NF-kappaB activation in the dorsal spinal cord. CB2 receptor stimulation decreased P2Y13 receptor expression via p38MAPK/NF-kappaB signaling. On the other hand, CB2 receptor activation decreased P2Y12 receptor expression via p38MAPK-independent NF-kappaB signaling pathway.http://link.springer.com/article/10.1186/s12974-017-0960-0CB2 receptorP2Y12 receptorP2Y13 receptorDorsal spinal cordMicrogliaNeuropathic pain |
| spellingShingle | Juan Niu Dujuan Huang Rui Zhou MingXia Yue Tao Xu Junna Yang Li He Hong Tian XiaoHong Liu Junwei Zeng Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats Journal of Neuroinflammation CB2 receptor P2Y12 receptor P2Y13 receptor Dorsal spinal cord Microglia Neuropathic pain |
| title | Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats |
| title_full | Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats |
| title_fullStr | Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats |
| title_full_unstemmed | Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats |
| title_short | Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats |
| title_sort | activation of dorsal horn cannabinoid cb2 receptor suppresses the expression of p2y12 and p2y13 receptors in neuropathic pain rats |
| topic | CB2 receptor P2Y12 receptor P2Y13 receptor Dorsal spinal cord Microglia Neuropathic pain |
| url | http://link.springer.com/article/10.1186/s12974-017-0960-0 |
| work_keys_str_mv | AT juanniu activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT dujuanhuang activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT ruizhou activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT mingxiayue activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT taoxu activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT junnayang activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT lihe activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT hongtian activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT xiaohongliu activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats AT junweizeng activationofdorsalhorncannabinoidcb2receptorsuppressestheexpressionofp2y12andp2y13receptorsinneuropathicpainrats |