Pharmacological modulation of secondary mediator systems–cyclic AMP and cyclic GMP–on inflammatory hyperalgesia

  title={Pharmacological modulation of secondary mediator systems–cyclic AMP and cyclic GMP–on inflammatory hyperalgesia},
  author={Fernando de Q Cunha and M. Menossi Teixera and Sérgio Henrique Ferreira},
  journal={British Journal of Pharmacology},
The objective of the present paper was to evaluate the relevance of neuronal balance of cyclic AMP and cyclic GMP concentration for functional regulation of nociceptor sensitivity during inflammation. Injection of PGE2 (10–100 ng paw−1) evoked a dose‐dependent hyperalgesic effect which was mediated via a cyclic AMP‐activated protein kinase (PKA) inasmuch as hyperalgesia was blocked by the PKA inhibitor H89. The PDE4 inhibitor rolipram and RP73401, but not PDE3 and PDE5 inhibitors potentiated… 

Peripheral and central activation of nitric oxide-cyclic GMP pathway by sildenafil

The results from the present study indicates that sildenafil has a central anti-nociceptive effect, which may be due to activation of the NO-cGMP pathway, as this effect was blocked by L-NAME and MB.

Contribution of 5- and 12-lipoxygenase products to mechanical hyperalgesia induced by prostaglandin E2 and epinephrine in the rat

Lipoxygenase products of arachidonic acid function as second messengers in the peripheral hyperalgesia induced by agents that act directly on primary afferent nociceptors (epinephrine and prostaglandin E2).

Low Nociceptor GRK2 Prolongs Prostaglandin E2 Hyperalgesia via Biased cAMP Signaling to Epac/Rap1, Protein Kinase Cε, and MEK/ERK

It is shown for the first time that prostaglandin E2-induced hyperalgesia is prolonged from <6 h in wild-type (WT) mice to 3 d in mice with low GRK2 in Nav1.8+ nociceptors (SNS–GRK2 +/− mice).

Involvement of NO–cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia

In carrageenan- and diabetes-induced hyperalgesia, TAD and L-NAME significantly increased paw withdrawal latencies (PWLs) as compared to the control group, suggesting an important role of NO–cGMP pathway in TAD-induced anti-hyperalgesic effect.

A Transient Receptor Potential Vanilloid 4-Dependent Mechanism of Hyperalgesia Is Engaged by Concerted Action of Inflammatory Mediators

It is concluded that TRPV4 plays a crucial role in the mechanical hyperalgesia that is generated by the concerted action of inflammatory mediators present in inflamed tissues.

A cascade of cytokines mediates mechanical inflammatory hypernociception in mice.

Results extend to mice the concept that the release of primary mediators responsible for hypernociception is preceded by a cascade of cytokines.



Peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway.

Mediation of primary afferent peripheral hyperalgesia by the cAMP second messenger system

Mediation of serotonin hyperalgesia by the cAMP second messenger system

Intracellular Messengers Contributing to Persistent Nociception and Hyperalgesia Induced by L‐Glutamate and Substance P in the Rat Formalin Pain Model

The results suggest that central sensitization and persistent nociception following formalin‐induced tissue injury, and the hyperalgesia in the formalin test induced by L‐glutamate and substance P, are dependent on the intracellular messengers nitric oxide, arachidonic acid and protein kinase C.

Characterization of prostanoid receptor‐evoked responses in rat sensory neurones

It is suggested that IP receptors play a major role in the sensitization of rat sensory neurones through a positive coupling of IP receptors to both adenylyl cyclase and phospholipase C in sensory neurone cells.

Prostaglandins facilitate peptide release from rat sensory neurons by activating the adenosine 3',5'-cyclic monophosphate transduction cascade

  • CM HingtgenKJ WaiteM. Vasko
  • Biology, Chemistry
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1995
It is demonstrated that the cAMP transduction cascade mediates the sensitizing actions of prostaglandins on peptide release from sensory neurons.