Induction of connexin 37 expression in a rat model of neuropathic pain

Lin, Sheng; Lu, Chengqiang; Muhammad, R.; Chou, Wen-Yi; Lin, Fun‐Chung; Wu, Pei‐Yu; Lin, Chia‐Jung; Yang, Lin

doi:10.1016/s0169-328x(02)00112-2

Cited by 20 publications

(10 citation statements)

References 14 publications

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“…Specifically, reduction of gap junction function under these conditions is correlated with decreased pain perception (38)(39)(40). Carbenoxolone, a nonselective gap junction inhibitor, produced analgesia in several experimental pain models (41,42).…”

Section: Discussionmentioning

confidence: 99%

Tramadol and Flurbiprofen Depress the Cytotoxicity of Cisplatin via Their Effects on Gap Junctions

Tong

Wang

et al. 2009

Clinical Cancer Research

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Purpose: Cancer patients are often concurrently treated with analgesics and antineoplastic drugs, yet the influence of analgesic agents on therapeutic activity of antineoplastic drugs is largely unexplored. This study investigates the effects of three commonly used analgesics, which produce analgesia by different mechanisms, on cytotoxicity induced by cisplatin, a widely used antitumor agent, and the relation between those effects and modulation of gap junction function by the analgesics. Experimental Design: The role of gap junctions in the modulation of cisplatin toxicity is explored by manipulation of connexin expression, and gap junction presence and function, using clinically relevant concentrations of the analgesics and cisplatin. Results: Short-term exposure of transformed cells to cisplatin reduced the clonogenic survival in low-density cultures (without gap junction formation) and in high density (with gap junction formation), but the toxic effect was greater at high density. In the absence of connexin expression or with block of connexin channels, cell density had no effect on cisplatin toxicity. Tramadol and flurbiprofen, but not morphine, significantly reduced cisplatin cytotoxicity, but this effect required functional gap junctions between the cells. Tramadol and flurbiprofen inhibited dye-coupling through gap junctions, but morphine did not. Conclusions:The results suggest that the density dependence of cisplatin toxicity is mediated by gap junctions. They further indicate that tramadol and flurbiprofen depress cisplatin cytotoxicity through inhibition of gap junction activity, and more generally, that agents that depress junctional communication can counteract the effects of antitumor agents. (Clin Cancer Res 2009;15(18):5803-10)

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Section: Discussionmentioning

confidence: 99%

Tramadol and Flurbiprofen Depress the Cytotoxicity of Cisplatin via Their Effects on Gap Junctions

Tong

Wang

et al. 2009

Clinical Cancer Research

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“…Although plasticity of peripheral gap junctions has been observed following nerve injury (Chandross et al, 1996;Nagaoka et al, 1999;Lin et al, 2002;Ohta et al, 2005), the evidence of their contribution to pain is very limited. A study by Lin et al (2002) suggested a role for Cx37 in neuropathic pain hypersensitivity following peripheral nerve injury through a correlation between the levels of sciatic nerve Cx37 mRNA and the extent of thermal hyperalgesia.…”

Section: Involvement Of Gap Junctions Inmentioning

confidence: 99%

“…A study by Lin et al (2002) suggested a role for Cx37 in neuropathic pain hypersensitivity following peripheral nerve injury through a correlation between the levels of sciatic nerve Cx37 mRNA and the extent of thermal hyperalgesia. A significant upregulation of endothelial Cx37 was found shortly after injury in the proximal and distal regions of the crushed sciatic nerve, lasting for up to 7 days and coinciding with the duration of injury-induced hyperalgesia (Lin et al, 2002). However, to date, there is no concrete evidence for a functional role of Cx37 in nociceptive transmission following nerve injury.…”

Section: Involvement Of Gap Junctions Inmentioning

confidence: 99%

Role of gap junctions in chronic pain

Green

Rupenthal

et al. 2011

J of Neuroscience Research

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Gap junctions are specialized transmembrane channels that allow rapid electrical signalling and direct intercellular communication for maintenance and coordination of normal cellular activities and homeostasis. Although gap junction channels in the nervous system mediate intercellular coupling between glial cells and between neurons, they also contribute to the spread of secondary damage and inflammation under pathological conditions. There is now evidence of the involvement of gap junctions in chronic pain caused by nervous system damage or tissue inflammation. In this Mini-Review, we highlight recent studies demonstrating the dynamic plasticity of gap junctions in response to nervous system injury and the effects of gap junction blockade on neuronal survival and modulation of pain in animal models of neuropathic and inflammatory pain. The involvement of dorsal root ganglia and spinal cord gap junctions in mediating chronic pain and the potential for targeting connexins as a novel modality for the treatment of intractable pain syndromes arising from nervous system injury and disorders are discussed.

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“…Previous work has documented that cellular injury is linked to an upregulation of Cx43 expression in a variety of cells and tissues (Daleau et al, 2001;VanSlyke and Musil, 2005). For example, alveolar epithelial cells increased Cx43 expression after radiation (Kasper et al, 1996), smooth muscle cells exhibited increased Cx43 levels after balloon catheter injury of rat carotid artery (Yeh et al, 1997), multiple Cxs were upregulated after peripheral nerve injury (Chandross, 1998;Chang et al, 2000;Lin et al, 2002), and one of the earliest responses to kidney damage is an increase of Cx43 expression (Yaoita et al, 2002). Similarly, Cx43 is upregulated after spinal cord injury (Theriault et al, 1997;Lee et al, 2005) and in cortical astrocytes exposed to ischemia (Cotrina et al, 1998a;Lin et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

A Central Role of Connexin 43 in Hypoxic Preconditioning

Lin

Lou²,

Kang³

et al. 2008

J. Neurosci.

155

134

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Preconditioning is an endogenous mechanism in which a nonlethal exposure increases cellular resistance to subsequent additional severe injury. Here we show that connexin 43 (Cx43) plays a key role in protection afforded by preconditioning. Cx43 null mice were insensitive to hypoxic preconditioning, whereas wild-type littermate mice exhibited a significant reduction in infarct volume after occlusion of the middle cerebral artery. In cultures, Cx43-deficient cells responded to preconditioning only after exogenous expression of Cx43, and protection was attenuated by small interference RNA or by channel blockers. Our observations indicate that preconditioning reduced degradation of Cx43, resulting in a marked increase in the number of plasma membrane Cx43 hemichannels. Consequently, efflux of ATP through hemichannels led to accumulation of its catabolic product adenosine, a potent neuroprotective agent. Thus, adaptive modulation of Cx43 can offset environmental stress by adenosine-mediated elevation of cellular resistance.

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Induction of connexin 37 expression in a rat model of neuropathic pain

Cited by 20 publications

References 14 publications

Tramadol and Flurbiprofen Depress the Cytotoxicity of Cisplatin via Their Effects on Gap Junctions

Tramadol and Flurbiprofen Depress the Cytotoxicity of Cisplatin via Their Effects on Gap Junctions

Role of gap junctions in chronic pain

A Central Role of Connexin 43 in Hypoxic Preconditioning

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