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| 1 | Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in descending pain facilitation显示文摘Objective Despite accumulating evidence on a role of immune cells and their associated chemicals in mechanisms of pain, few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain. The present study was undertaken to test the hypothesis that the chemokine (C-C motif) ligand 2 (CCL2) (commonly known as monocyte chemoattractant protein-1) signaling in the rostral ventromedial medulla (RVM), a pivotal structure in brainstem pain modulatory circuitry, is involved in descending pain facilitation in rats. Methods An L5 spinal nerve ligation (SNL) was produced in rats under pentobarbital anesthesia. Western blot and immunohistochemistry were used to detect the expression levels of CCL2 and CCL2 receptor (CCR2), and examine their distributions compared with the neuronal marker NeuN as well as glial markers glial fibrillary acidic protein (GFAP, astroglial) and CD11b (microglial), respectively. Results SNL induced an increase in CCL2 expression in the RVM, and this returned to the control level at 4 weeks after injury. The induced CCL2 colocalized with NeuN, but not with GFAP and CD11b. CCR2 was also upregulated by SNL in the RVM, and this increase lasted for at least 4 weeks. CCR2 was colocalized with CD11b but not GFAP. Few RVM neurons also exhibited CCR2 staining. Neutralizing CCL2 with an anti-CCL2 antibody (0.2–20 ng) or injecting RS-102895 (0.1–10 pmol), a CCR2b chemokine receptor antagonist, into the RVM on day 1 after SNL, significantly attenuated the established thermal and mechanical hypersensitivity. In addition, injection of recombinant rat CCL2 (0.03–3 pmol) into the RVM induced dose-dependent hyperalgesia, which was prevented by pretreatment with RS-102895 (10 pmol). Interleukin-1β (IL-1β), a potent inducer of neuronal CCL2, was also selectively upregulated in RVM reactive astrocytes. Injection of IL-1β (120 fmol) into the RVM induced behavioral hyperalgesia, which was blocked by RS-102895 (10 pmol). However, an IL-1 receptor antagonist (3 pmol) did not prevent CCL2 (3 pmol)-induced hyperalgesia. These results suggest that the effect of CCL2 is downstream to IL-1β signaling. Conclusion The IL-1β and CCL2-CCR2 signaling cascades play a role in neuron-glia-cytokine interactions and the descending facilitation of neuropathic pain. | Ronald Dubner | 2012 | Neuroscience Bulletin2012，28，2： | 6 |
| 2 | Predicting gallstone pancreatitis with laboratory parameters:a meta-analysis显示文摘 | Tenner S Dubner H Steinberg W | | 0，，10： | 1 |
| 3 | Osteoarthritis pain mechanisms: basic studies in animal models 显示文摘 | Zhang RX Ren K Dubner R | 2013 | Osteoarthritis Cartilage2013，21，9： | 1 |
| 4 | A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia显示文摘 | Hargreaves K Dubner R Brown F | 1988 | Pain1988，32，1： | 1 |
| 5 | Idiopathic trigeminal neu- ralgia: sensory features and pain mechanisms显示文摘 | Dubner R Sharav Y Gracely RH | 1987 | Pain1987，31，： | 1 |
| 6 | Pain measure- ment: an overview 显示文摘 | Chapman CR Casey KL Dubner R | 1985 | Pain1985，22，1： | 1 |
| 7 | A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia 显示文摘 | HARGREAVES K DUBNER R BROWN F | 1988 | Pain1988，32，1： | 1 |
| 8 | A new and sensitive method for measuring thermal, nociception in cutaneous hyperalgesia显示文摘 | HARGREAVES K DUBNER R BROWN F | 1988 | Pain1988，32，1： | 1 |
| 9 | Persistent Fos protein expression after orofacial deep or cutaneous tissue inflammationin rats: implications for persistent orofacial pain 显示文摘 | Zhou QQ Imbe H Dubner R | 1999 | J Comp Neurol1999，412，2： | 1 |
| 10 | A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia显示文摘 | Hargreaves K Dubner R Brown F | 1988 | Pain1988，32，1： | 1 |
| 11 | A new and sensi-tive method for measuring thermal nociception in cutaneoushyperalgesia 显示文摘 | Hargreaves K Dubner R Brown F | 1998 | Pain1998，32，1： | 1 |
| 12 | A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia显示文摘 | Hargreaves K Dubner R Brown F | 1988 | Pain1988，32，1： | 1 |
| 13 | Neurocytoma of the cerebellum显示文摘 | Ogiwara H Dubner S Biqio E | 2011 | Surg Neurol Int2011，2，： | 1 |
| 14 | A new and sensitive method for measuring thermal nocieeption in cutaneous hyperalge- sia显示文摘 | Hargreaves K Dubner R Brown F | 1998 | Pain1998，32，1： | 1 |
| 15 | A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia 显示文摘 | Hargreaves K Dubner R Brown F | 1988 | Pain1988，32，： | 1 |
| 16 | A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury 显示文摘 | Seltzer Z Dubner R Shir Y | 1990 | Pain1990，43，： | 1 |
| 17 | A new and sensitive method for measuring thermal in cutaneous hyperalgesia 显示文摘 | Hargreaves K Dubner R Brown F | 1988 | Pain1988，32，1： | 1 |
| 18 | Idiopathic trigeminal neuralgia: sensory features and pain mechanism 显示文摘 | Dubner R Sharav Y Gracely R H | 1987 | Pain1987，31，： | 1 |
| 19 | A new and sensitive method for mearing thermal nociception in cutaneous hyperalgesia显示文摘 | Hargeaves K Dubner R Brown F | | 0，，1： | 1 |
| 20 | Predicting gallstone pancreatitis with laboratory parameters: a meta-analysis显示文摘 | Tenner S Dubner H Steinberg W | 1994 | An J Gastroenterol1994，89，10： | 1 |
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