Inhibition of the Cyclic Adenosine Monophosphate Pathway Attenuates Neuropathic Pain and Reduces Phosphorylation of Cyclic Adenosine Monophosphate Response Element-Binding in the Spinal Cord After Partial Sciatic Nerve Ligation in Rats

Department of Anesthesiology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
Anesthesia and analgesia (Impact Factor: 3.47). 01/2008; 105(6):1830-7, table of contents. DOI: 10.1213/01.ane.0000287652.42309.5c
Source: PubMed


Recent reports have identified a role for cyclic adenosine monophosphate (cAMP) transduction in nociceptive processing. Spinal activation of the cAMP induced gene transcription through the activation of protein kinase A and cAMP response element-binding protein (CREB). Intrathecal injection of protein kinase A inhibitor reversed the mechanical hyperalgesia, whereas injection of CREB antisense attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. In the present study, we aimed to assess the effects of spinal cAMP transduction on the nociceptive processing in a chronic neuropathic pain model.
PSNL was performed in male Sprague-Dawley rats 1 wk after intrathecal catheterization. Nociception to mechanical and thermal stimuli was assessed at the hindpaw 2 h, 3, 7, and 14 days after PSNL. The effects of adenylate cyclase inhibitor, SQ22536 (0.7 mumol, intrathecal) on these nociceptions were evaluated. Changes in the expression and immunoreactivity of CREB and its phosphorylated proteins (CREB-IR and pCREB-IR) in the dorsal horn of the spinal cord were also measured.
The expression of CREB-IR and pCREB-IR proteins was shown to increase for 2 wk after PSNL. The increase in pCREB was partially reversed by the blockade of the cAMP pathway in the early 3 days, with a parallel increase in mechanical and thermal withdrawal thresholds.
These results revealed the possible contribution of an increase in pCREB to the PSNL-induced tactile allodynia and thermal hyperalgesia. Modulation of the cAMP pathway may be clinically relevant if early intervention can be achieved in patients with chronic neuropathic pain.

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Available from: Jiin-Tarng Liou, Jun 09, 2014
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    • "The down-stream effectors of the adenylate cyclase/cAMP pathway were evaluated by determining the phosphorylation of the transcription factor CREB (pCREB) at Ser133 (Gonzalez et al., 1989), which is upregulated in numerous animal models for pain (Hoeger-Bement and Sluka, 2003; Ji and Rupp, 1997; Liou et al., 2007). Consistent with the decrease in cAMP levels, light exposure Fig. 2. Photostimulation of optoMOR inhibits Ca 2 þ influx. "
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    • "The A 2A Rs stimulation produces an increase in the intracellular levels of the cyclic adenosine monophosphate (cAMP). In this line, a recent study shows that the inhibition of cAMP pathway attenuates the behavioural symptoms of neuropathic pain and reduces phosphorylation of cyclic adenosine monophosphate response element-binding in the spinal cord after partial sciatic nerve ligation in rats [35]. This study contributes to a better understanding of the function of A 2A Rs in pain modulation and demonstrates the crucial role of these receptors in the control of neuropathic pain at the spinal cord level. "
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