2013
DOI: 10.1016/j.jpain.2012.11.002
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Spinal Astrocyte Gap Junctions Contribute to Oxaliplatin-Induced Mechanical Hypersensitivity

Abstract: Spinal glial cells contribute to the development of many types of inflammatory and neuropathic pain. Here the contribution of spinal astrocytes and astrocyte gap junctions to oxaliplatin-induced mechanical hypersensitivity was explored. The expression of glial fibrillary acidic protein (GFAP) in spinal dorsal horn was significantly increased at day 7 but recovered at day 14 after oxaliplatin treatment, suggesting a transient activation of spinal astrocytes by chemotherapy. Astrocyte-specific gap junction prote… Show more

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Cited by 111 publications
(104 citation statements)
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References 59 publications
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“…Similar to the current findings, a previous study demonstrated that siRNA-induced knockdown of Cx43 in the trigeminal ganglion of naïve rats evoked facial mechanical hypersensitivity (Ohara et al, 2008). At the same time, however, increased Cx43 expression in the spinal cord has been observed following chronic constriction injury (CCI) and oxaliplatin -induced peripheral neuropathy (Chen et al, 2014;Spataro et al, 2004;Yoon et al, 2013). There are likely functional distinctions of Cx43 expressed in trigeminal ganglia vs. spinal dorsal horn and possible differences in the role of Cx43 in each peripheral neuropathy model (PSNL in the current study vs. CCI and oxaliplatin-induced neuropathy in previous studies).…”
Section: Discussionsupporting
confidence: 89%
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“…Similar to the current findings, a previous study demonstrated that siRNA-induced knockdown of Cx43 in the trigeminal ganglion of naïve rats evoked facial mechanical hypersensitivity (Ohara et al, 2008). At the same time, however, increased Cx43 expression in the spinal cord has been observed following chronic constriction injury (CCI) and oxaliplatin -induced peripheral neuropathy (Chen et al, 2014;Spataro et al, 2004;Yoon et al, 2013). There are likely functional distinctions of Cx43 expressed in trigeminal ganglia vs. spinal dorsal horn and possible differences in the role of Cx43 in each peripheral neuropathy model (PSNL in the current study vs. CCI and oxaliplatin-induced neuropathy in previous studies).…”
Section: Discussionsupporting
confidence: 89%
“…There is currently no evidence that nociceptive hypersensitivity is reversed by decreasing Cx43 expression in spinal dorsal horn to basal levels. It has been shown, though, that gap junction inhibitors significantly ameliorate neuropathic pain due to a CCI or oxaliplatin-induced peripheral neuropathy (Chen et al, 2014;Spataro et al, 2004;Yoon et al, 2013). Interestingly, the current study also showed that markedly increased expression of Cx43 from basal levels in uninjured animals, similar to that observed following a CCI or oxaliplatin treatment, led to significant mechanical hypersensitivity.…”
Section: Discussionsupporting
confidence: 68%
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“…While downregulation of Cx43 expression leads to cutaneous hypersensitivity, increased Cx43 also leads to cutaneous hypersensitivity. Increased Cx43 expression in the spinal cord has been reported in a number of rodent neuropathic pain models [7,24]. Based on our previous and current findings, we suggest that what is more important is that absolute change in spinal Cx43 expression leads to the neuropathic state-the direction of change appears to be etiologically dependent.…”
Section: Discussionsupporting
confidence: 74%
“…It has already been shown that the action of oxaliplatin occurs only in myelinated fibers, since oxaliplatin induced bursts of action potentials in myelinated A-fibers, but not in unmyelinated C-fibers (Sittl et al, 2010). Additionally, recent studies have shown that oxaliplatin can affect the expression levels of GJs in astrocytes (Yoon et al, 2013) and dorsal root ganglia (DRG) satellite glial cells (Warwick and Hanani, 2013), while GJ blockage by carbenoxolone results in analgesic-like effects (Rouach et al, 2003;Vessey et al, 2004). Furthermore, GJ hemichannel blockade was found to be neuroprotective in some cases of global cerebral ischemia in nearterm fetal sheep (Davidson et al, 2014), while gap junctional communication could counteract the effects of the anti-tumor agent cisplatin (homologous to oxaliplatin) (Broomand et al, 2009).…”
Section: Introductionmentioning
confidence: 99%