Pain and analgesia: The dual effect of nitric oxide in the nociceptive system

Cury, Yara; Picolo, Gisele; Gutierrez, Vanessa Pacciari; Ferreira, Sérgio Henrique

doi:10.1016/j.niox.2011.06.004

Cited by 251 publications

(231 citation statements)

References 170 publications

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“…NO reduces inflammation and edema by inhibiting nociceptive signaling formation in the spinal cord (Brock and Tonussi, 2008;Cury et al, 2011;Foletto et al, 2013). This is consistent with our observations that IMPOC promotes the activity of several molecular components important for the NOS signaling pathway, and intrathecal NOS inhibitors prevented the IMPOC therapeutic effect and IMPOC enhancement of NOS signaling.…”

Section: Discussionsupporting

confidence: 92%

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Spinal Neuronal NOS Signaling Contributes to Morphine Cardioprotection in Ischemia Reperfusion Injury in Rats

Jiang

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Morphine has been widely used as rescue treatment for heart attack and failure in humans for many decades. Relatively little has been known about the role of spinal opioid receptors in morphine cardioprotection. Recent studies have shown that intrathecal injection of morphine can reduce the heart injury caused by ischemia (I)/reperfusion (R) in rats. However, the molecular and cellular mechanisms underlying intrathecal morphine cardioprotection has not been determined. Here, we report that intrathecal morphine postconditioning (IMPOC) rescued mean artery pressure (MAP) and reduced myocardial injury in I/R. Pretreatment with either naloxone (NAL), a selective muopioid receptor antagonist, or nitric oxide synthase (NOS) inhibitors via intrathecal delivery completely abolished IMPOC cardioprotection, suggesting that the spinal mu-opioid receptor and its downstream NOS signaling pathway are involved in the mechanism of the morphine-induced effect. Consistent with this, IMPOC significantly enhanced spinal neural NOS phosphorylation, nitric oxide, and cGMP content in a similar time course. Intrathecal application of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of guanylate cyclase, completely ablated IMPOC-induced enhancement of cardioprotection and spinal cGMP content. IMPOC rescue of MAP and ischemic injury is correlated with IMPOC enhancement of NOS signaling. Collectively, these findings strengthen the concept of spinal mu-opioid receptors as a therapeutic target that mediates morphine-induced cardioprotection. We also provide evidence suggesting that the activation of spinal NOS signaling is essential for morphine cardioprotection.

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Section: Discussionsupporting

confidence: 92%

“…NO is synthesized by the NOS from L-arginine and different cofactors. Neuronal NOS (nNOS) is the predominant form of NOS expressed in the brain and spinal cord (Cury et al, 2011). Intrathecal application of an opioid agonist, fentanyl, in preconditioning was found to reduce I/R injury in rats (Lu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Spinal Neuronal NOS Signaling Contributes to Morphine Cardioprotection in Ischemia Reperfusion Injury in Rats

Jiang

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…NO is a constantly synthesized soluble gas from L-arginine amino acid in endothelial cells by the nitric oxide synthase (NOS) enzyme (Mayer and Hemmens 1997). Nitric oxide is known to play a complex part in transmission of nociceptive signals peripherally and centrally (Cury et al 2011;Galdino et al 2015). Nitric oxide is known to be involved in the inhibition of neurons that are spontaneously activated in response to pain and particularly diminishing the activity of pain mediators such as substance P released in spinal cord (Garry et al 1994;Schmid and Pehl 1996).…”

Section: Discussionmentioning

confidence: 99%

Possible mechanisms involved in the anti-nociceptive effects of hydro-ethanolic leaf extract ofZiziphus abyssinica

Boakye‐Gyasi

Henneh

Abotsi

et al. 2017

Pharmaceutical Biology

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Context: Various parts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) have been used in Ghanaian and African traditional medicine as an analgesic. However, there are little scientific data to support the anti-nociceptive effects of the hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) as well as the possible mechanisms involved in its anti-nociceptive effects. Purpose: To predict possible nociceptive pathways involved in the anti-nociceptive effects of EthE. Materials and methods: The effect of EthE (30, 100 and 300 mg/kg) on intraplantar injection of pain mediators such as interleukin-1b, tumour necrosis factor-a, prostaglandin E 2 and bradykinin was evaluated in male Sprague Dawley rats using Randall-Selitto test for 5 h. The effect of specific antagonists to the opioidergic, adenosinergic, ATP-sensitive K þ channels, nitric oxide, serotonergic, muscarinic, adrenergic and voltage-gated calcium channel on the anti-nociceptive effect of EthE (100 mg/kg) was evaluated using the formalin test in male imprinting control region (ICR) mice for 1 h. Results: Pretreatment of the rats with EthE significantly reversed the hypernociception induced by intraplantar injection of TNF-a (F 4,120 ¼ 10.86, p < 0.0001), IL-1b (F 4,120 ¼ 14.71, p < 0.0001), bradykinin (F 4,80 ¼ 12.52, p < 0.0001) and prostaglandin E 2 (F 5,144 ¼ 6.165, p ¼ 0.0001). The anti-nociceptive effect exhibited by EthE in the formalin test was reversed by systemic administration of N G -L-nitro-arginine methyl ester, naloxone, theophylline and glibenclamide. Conclusions: EthE inhibits hypernociception induced by TNF-a, IL-1b, bradykinin and prostaglandin E 2 . EthE exhibited anti-nociceptive effects possibly mediated through opioidergic, adenosinergic, ATP-sensitive potassium channels and nitric oxide cyclic GMP pathways. ARTICLE HISTORY

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“…On the other hand, the role of NO in the development of nociception is not suffi ciently understood. One thing is for sure that NO has dual nociceptive effect, which depends on the location of its production (local -at the site of infl ammation or at the level of the spinal cord), and the produced amounts of NO [35].…”

Section: Discussionmentioning

confidence: 99%

L-Arginine-No System Participates in the Analgesic Effect of Flunixin Meglumine in the Rat

et al. 2016

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This study investigated whether the L-arginine-NO system participates in the analgesic effect of fl unixin meglumine in the rat. Hyperalgesia was induced by intraplantar (i.pl.) administration of carrageenan (500 μg) into the rat's hind paw. Electronic von Frey apparatus was used to determine paw withdrawal threshold induced by pressure as the painful stimulus, measured in grams (g). Flunixin meglumine (FM; 0.09-0.1 mg/kg; s.c.) and N G -nitro-L-arginine methyl ester (L-NAME; 10 mg/kg; i.p.), given separately as a pre-treatment, i.e. 15 min before i.pl. injection of carrageenan, produced a signifi cant antinociception. When FM (0.09 mg/kg) and a sub-effective dose of L-NAME (5 mg/kg) were co-administered, the antinociceptive effect was signifi cantly increased in comparison with the effect of FM alone. L-arginine (L-ARG;10 mg/kg; i.p.) itself did not produce signifi cant effect on carrageenan-induced hyperalgesia, but signifi cantly reduced the antinociceptive effects of both FM and FM + L-NAME combination. The inhibition of the production of NO might be involved in the mechanism of the analgesic effect of FM.

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Pain and analgesia: The dual effect of nitric oxide in the nociceptive system

Cited by 251 publications

References 170 publications

Spinal Neuronal NOS Signaling Contributes to Morphine Cardioprotection in Ischemia Reperfusion Injury in Rats

Spinal Neuronal NOS Signaling Contributes to Morphine Cardioprotection in Ischemia Reperfusion Injury in Rats

Possible mechanisms involved in the anti-nociceptive effects of hydro-ethanolic leaf extract ofZiziphus abyssinica

L-Arginine-No System Participates in the Analgesic Effect of Flunixin Meglumine in the Rat

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