Increases in the phosphorylation of cyclic AMP response element binding protein (CREB) and decreases in the content of calcineurin accompany thermal hyperalgesia following chronic constriction injury in rats

Miletić, Gordana; Pankratz, Matthew; Miletić, Vjekoslav

doi:10.1016/s0304-3959(02)00242-7

Cited by 87 publications

(87 citation statements)

References 19 publications

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“…As in other models of neuropathy (Ma and Quirion, 2001;Miletic et al, 2002;Song et al, 2005;Crown et al, 2006), the expression of the phosphorylated form of the CREB transcription factor significantly increased in the ipsilateral dorsal horn of SNL animals (Fig. 9, SNL, black bars), both in superficial and deep laminae (respectively ϩ21.0 Ϯ 2.8% and ϩ21.4 Ϯ 2.0% compared to contralateral dorsal horn).…”

Section: Ca V 12-dependent Gene Activationsupporting

confidence: 75%

Knockdown of L Calcium Channel Subtypes: Differential Effects in Neuropathic Pain

Fossat¹,

Dobremez²,

Bouali‐Benazzouz³

et al. 2010

J. Neurosci.

101

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The maintenance of chronic pain states requires the regulation of gene expression, which relies on an influx of calcium. Calcium influx through neuronal L-type voltage-gated calcium channels (LTCs) plays a pivotal role in excitation-transcription coupling, but the involvement of LTCs in chronic pain remains unclear. We used a peptide nucleic acid (transportan 10-PNA conjugates)-based antisense strategy to investigate the role of the LTC subtypes Ca V 1.2 and Ca V 1.3 in long-term pain sensitization in a rat model of neuropathy (spinal nerve ligation). Our results demonstrate that specific knockdown of Ca V 1.2 in the spinal dorsal horn reversed the neuropathy-associated mechanical hypersensitivity and the hyperexcitability and increased responsiveness of dorsal horn neurons. Intrathecal application of anti-Ca V 1.2 siRNAs confirmed the preceding results. We also demonstrated an upregulation of Ca V 1.2 mRNA and protein in neuropathic animals concomitant to specific Ca V 1.2-dependent phosphorylation of the cAMP response element (CRE)-binding protein (CREB) transcription factor. Moreover, spinal nerve ligation animals showed enhanced transcription of the CREB/CRE-dependent gene COX-2 (cyclooxygenase 2), which also depends strictly on Ca V 1.2 activation. We propose that L-type calcium channels in the spinal dorsal horn play an important role in pain processing, and that the maintenance of chronic neuropathic pain depends specifically on channels comprising Ca V 1.2.

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Section: Ca V 12-dependent Gene Activationsupporting

confidence: 75%

Knockdown of L Calcium Channel Subtypes: Differential Effects in Neuropathic Pain

Fossat¹,

Dobremez²,

Bouali‐Benazzouz³

et al. 2010

J. Neurosci.

101

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“…19,23,24 Those rats who suffered from neuropathic pain demonstrated a similar phenomenon. 12,25 In contrast, Miletic et al reported that there were no differences in CREB content between control and study animals. 25 In fact, the effect of adenylate cyclase inhibitor on inflammatory response remains a topic for investigation.…”

Section: Discussionmentioning

confidence: 91%

Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats

Liou

Liu

Mao

et al. 2009

Can J Anesth/J Can Anesth

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Purpose There is evidence that cyclic adenosine monophosphate (cAMP) transduction is involved in nociceptive processing. We previously showed that intrathecal injection of an adenylate cyclase inhibitor attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. The present study investigates the pre-emptive effects of spinal cAMP transduction on nociceptive processing in a chronic neuropathic pain model. Methods Intrathecal catheterization and PSNL were performed in male Sprague-Dawley rats. Nociceptive responses to mechanical and thermal stimuli were evaluated at the hindpaw at 2 hr and at 3, 7, and 14 days after PSNL. The pre-emptive effects of the intrathecal adenylate cyclase inhibitor, SQ22536 (0.7 lmol Á L -1 , 30 min before or after nerve ligation) were assessed. Also, the spatial and temporal expression profiles and immunoreactivity in the spinal cord of the cAMP response element binding protein (CREB) and its phosphorylated proteins (CREB-IR and p-CREB-IR) were analyzed.Results Compared with the rats treated with the vehicle, allodynia and hyperalgesia were significantly attenuated at 1-3 days by the intrathecal injection of SQ22536 performed either before or after ligation. The expression of CREB was significantly higher after ligation (P \ 0.05), but differences were not observed between groups. Intrathecal injection of SQ22536, either before or after ligation, partially reduced p-CREB-IR protein expression in comparison with the vehicle control, especially after the first 3 days (P \ 0.05). Conclusion Our results show a possible association between the increase in p-CREB and PSNL-induced neuropathic pain. However, a pre-emptive effect of adenylate cyclase inhibitor administered before surgery was not observed. RésuméObjectif Des donne´es soutiennent que la transduction de l'ade´nosine monophosphate cyclique (AMPc) est implique´e dans le traitement des signaux nociceptifs. Nous avons pre´ce´demment montre´que l'injection intrathe´cale d'un inhibiteur de l'ade´nylcyclase atte´nuait l'allodynie tactile cause´e par une ligature partielle du nerf sciatique (PSNL) chez le rat. Cette e´tude explore les effets pre´ventifs de la transduction d'AMPc rachidienne sur le traitement des signaux nociceptifs dans un mode`le de douleur neuropathique chronique. Méthode Un cathe´te´risme intrathe´cal et une PSNL ont e´te´re´alise´s sur des rats maˆles Sprague-Dawley. Les re´actions nociceptives aux stimuli me´caniques et thermiques ont e´te´e´value´es a`la patte arrie`re a`2 heures et a`3, 7 et 14 jours post-PSNL. Les effets pre´ventifs de l'inhibiteur intrathe´cal de l'ade´nylcyclase, le SQ22536, (0.7 lmolÁL -1 , 30 min avant ou apre`s la ligature du nerf) ont e´te´e´value´s. De plus, les profils d'expression spatiale et temporelle et

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“…A ativação de PKR por estímulos extracelulares ocorre, principalmente, pelos receptores da família TLR (Toll-like receptor) através da ligação com RNAds, lipopolisacarídeo (LPS), e peptídeoglicanos (Mannion et al, 1999;Miletic, Hanson e Miletic, 2004;Miletic, Hanson, Savagian, et al, 2004) desempenhando, assim, uma ação preponderante na ativação da resposta imune inata (Mcguire et al, 1997;Mantyh et al, 2002;Miletic et al, 2002;Miyabe e Miletic, 2005). Sabemos, hoje, que PKR sinaliza também em resposta, fatores de crescimento, como o Fator de Crescimento Derivado de Plaquetas (PDGF, platelet-derived gowth factor) e citocinas como o interferon, interleucina-1 (IL-1) e o Fator de necrose tumoral-α (TNF-α, tumor necrosis factor) (Mcguire et al, 1997;Mantyh et al, 2002;Miletic et al, 2002;Miyabe e Miletic, 2005).…”

Section: Ativação Da Pkrunclassified

“…Sabemos, hoje, que PKR sinaliza também em resposta, fatores de crescimento, como o Fator de Crescimento Derivado de Plaquetas (PDGF, platelet-derived gowth factor) e citocinas como o interferon, interleucina-1 (IL-1) e o Fator de necrose tumoral-α (TNF-α, tumor necrosis factor) (Mcguire et al, 1997;Mantyh et al, 2002;Miletic et al, 2002;Miyabe e Miletic, 2005).…”

Section: Ativação Da Pkrunclassified

“…Outro alvo são proteínas da família STAT (Signal Transducers and Activators of Transcription), proteínas envolvidas em diversas funções biológicas e que participam ativamente das vias de sinalização intracelular desencadeadas por interferons e outras citocinas (Pace et al, 1997;Miletic et al, 2002;Miletic, Hanson e Miletic, 2004;Miletic, Hanson, Savagian, et al, 2004).…”

Section: Regulação De Sinalização Intracelular Da Pkrunclassified

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Efeito do tratamento quimioterápico sobre a ação da proteína quinase dependente de RNA (PKR) nos sistemas nociceptivo e muscular

Carvalho¹

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Increases in the phosphorylation of cyclic AMP response element binding protein (CREB) and decreases in the content of calcineurin accompany thermal hyperalgesia following chronic constriction injury in rats

Cited by 87 publications

References 19 publications

Knockdown of L Calcium Channel Subtypes: Differential Effects in Neuropathic Pain

Knockdown of L Calcium Channel Subtypes: Differential Effects in Neuropathic Pain

Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats

Efeito do tratamento quimioterápico sobre a ação da proteína quinase dependente de RNA (PKR) nos sistemas nociceptivo e muscular

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