Impaired nocifensive behaviours and mechanical hyperalgesia, but enhanced thermal allodynia in pituitary adenylate cyclase-activating polypeptide deficient mice

Sándor, Katalin; Kormos, Viktória; Botz, Bálint; Imreh, András; Bölcskei, Kata; Gaszner, Balázs; Markovics, Adrienn; Szolcsányi, Janós; Shintani, Norihito; Hashimoto, Hitoshi; Baba, Akemichi; Reglődi, Dóra; Helyes, Zsuzsanna

doi:10.1016/j.npep.2010.06.004

Cited by 45 publications

(37 citation statements)

References 46 publications

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“…Thereafter the wound was closed, and the animals were not examined for the next 7 days in order not to disturb the healing process. In accordance with our previous studies [42,44], this is a reliable model of neuropathic mechanical hyperalgesia, which is not influenced by an impaired weight distribution.…”

Section: The Traumatic Mononeuropathy Modelsupporting

confidence: 91%

“…Thermal allodynia mediated only by peripheral mechanisms is increased in PACAP gene-deficient animals, but somatic and visceral nocifensive behaviors, and neuropathic mechanical hyperalgesia are diminished. This demonstrates that PACAP can have both inhibitory and excitatory roles depending on the site of action and the predominant mechanism in the pain model [44].…”

Section: Introductionmentioning

confidence: 91%

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Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

et al. 2013

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a b s t r a c tPituitary Adenylate-Cyclase Activating Polypeptide (PACAP) and Tac1 gene-encoded tachykinins (substance P: SP, neurokinin A: NKA) are expressed in capsaicin-sensitive nerves, but their role in nociception, inflammation and vasoregulation is unclear. Therefore, we investigated the function of these neuropeptides and the NK 1 tachykinin receptor (from Tacr1 gene) in the partial sciatic nerve ligationinduced traumatic mononeuropathy model using gene deficient (PACAP −/− , Tac1 −/− , and Tacr1 −/− ) mice. Mechanonociceptive threshold of the paw was measured with dynamic plantar aesthesiometry, motor coordination with Rota-Rod and cutaneous microcirculation with laser Doppler imaging. Neurogenic vasodilation was evoked by mustard oil stimulating sensory nerves. In wildtype mice 30-40% mechanical hyperalgesia developed one week after nerve ligation, which was not altered in Tac1−/− and Tacr1mice, but was absent in PACAP −/− animals. Motor coordination of the PACAP −/− and Tac1 −/− groups was significantly worse both before and after nerve ligation compared to their wildtypes, but it did not change in Tacr1−/− mice. Basal postoperative microcirculation on the plantar skin of PACAP −/− mice did not differ from the wildtypes, but was significantly lower in Tac1 −/− and Tacr1 −/− ones. In contrast, mustard oil-induced neurogenic vasodilation was significantly smaller in PACAP −/− mice, but not in Tacr1 −/− and Tac1 −/− animals. Both PACAP and SP/NKA, but not NK 1 receptors participate in normal motor coordination. Tachykinins maintain basal cutaneous microcirculation. PACAP is a crucial mediator of neuropathic mechanical hyperalgesia and neurogenic vasodilation. Therefore identifying its target and developing selective, potent antagonists, might open promising new perspectives for the treatment of neuropathic pain and vascular complications.

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Section: The Traumatic Mononeuropathy Modelsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 91%

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

et al. 2013

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“…Mice lacking PACAP are temperature-sensitive (Gray et al 2002), have decreased fertility and reproductive functions (Isaac and Sherwood 2008), display early neonatal death (Cummings et al 2004), and react to hormonal and metabolic changes in an altered manner (Hatanaka et al 2008;Nakata et al 2004;Tomimoto et al 2008). Furthermore, PACAP deficient mice have memory disturbances, abnormal nonvisual photoreception, behavioral abnormalities, and altered pain and inflammatory reactions (Hashimoto et al 2001Kawaguchi et al 2010;Kemeny et al 2010;Matsuyama et al 2003;Sandor et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Mice Deficient in Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) are More Susceptible to Retinal Ischemic Injury In Vivo

et al. 2011

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroprotective peptide exerting protective effects in neuronal injuries. We have provided evidence that PACAP is neuroprotective in several models of retinal degeneration in vivo. Our previous studies showed that PACAP treatment ameliorated the damaging effects of chronic hypoperfusion modeled by permanent bilateral carotid artery occlusion. We have also demonstrated in earlier studies that treatment with PACAP antagonists further aggravates retinal lesions. It has been shown that PACAP deficient mice have larger infarct size in cerebral ischemia. The aim of this study was to compare the degree of retinal damage in wild type and PACAP deficient mice in ischemic retinal insult. Mice underwent 10 min of bilateral carotid artery occlusion followed by 2-week reperfusion period. Retinas were then processed for histological analysis. It was found that PACAP deficient mice had significantly greater retinal damage, as shown by the thickness of the whole retina, the morphometric analysis of the individual retinal layers, and the cell numbers in the inner nuclear and ganglion cell layers. Exogenous PACAP administration could partially protect against retinal degeneration in PACAP deficient mice. These results clearly show that endogenous PACAP reacts as a stress-response peptide that is necessary for endogenous protection against different retinal insults.

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“…The role of PACAP in vasodilatation [57,58] and nociceptive processes [59][60][61][62][63][64][65] has been confirmed in several studies. The presence of this peptide has been demonstrated in the trigeminal system [35,[66][67][68].…”

Section: Pacap -Neuropeptides Nociception Trigeminal System Migrainementioning

confidence: 76%

“…Moreover, PACAP release in the dorsal horn has been reported in other experimental conditions of peripheral stimulation [126][127][128][129][130]. The potential relationship between PACAP and pain is enhanced by the co-localization and functional link of the NOS and PACAP systems, which has been described in a variety of studies [63,76,[131][132][133][134].…”

Section: Chemical Stimulation Of the Tsmentioning

confidence: 85%

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

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Impaired nocifensive behaviours and mechanical hyperalgesia, but enhanced thermal allodynia in pituitary adenylate cyclase-activating polypeptide deficient mice

Cited by 45 publications

References 46 publications

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

Mice Deficient in Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) are More Susceptible to Retinal Ischemic Injury In Vivo

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

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