PPADS, a purinergic antagonist reduces Fos expression at spinal cord level in a mouse model of mononeuropathy

Borsani, Elisa; Albertini, Roberta; Colleoni, Mariapia; Sacerdote, Paola; Trovato, Anna Elisa; Lonati, Claudio; Labanca, Mauro; Panerai, Alberto E.; Rezzani, Rita; Rodella, Luigi Fabrizio

doi:10.1016/j.brainres.2007.12.066

Cited by 9 publications

(8 citation statements)

References 56 publications

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“…In line with the present study, localized application of PPADS effectively attenuated carrageenan‐ or postoperative‐induced spontaneous nociceptive responses in rats . In addition, intrathecal or systemic administration of PPADS markedly suppressed formalin and chronic nerve constriction nociceptive responses induced by injuries in mice . Moreover, peripheral P2X 3 and P2Y receptors are involved in the maintenance of melittin‐induced persistent pain, as melittin is the major component (50%) of BV and contributes to the BV‐evoked nociception .…”

Section: Discussionsupporting

confidence: 88%

“…24,25 In addition, intrathecal or systemic administration of PPADS markedly suppressed formalin and chronic nerve constriction nociceptive responses induced by injuries in mice. 16,[26][27][28] Moreover, peripheral P2X 3 and P2Y receptors are involved in the maintenance of melittin-induced persistent pain, 29 as melittin is the major component (50%) of BV and contributes to the BV-evoked nociception. 10,[30][31][32] The results of the present study support the findings described above.…”

Section: Discussionmentioning

confidence: 99%

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Role of peripheral purinoceptors in the development of bee venom‐induced nociception: A behavioural and electrophysiological study in rats

Luo

Fan

et al. 2014

Clin Exp Pharma Physio

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Colocalization of purinergic P2X and P2Y receptors in dorsal root ganglion sensory neurons implies that these receptors play an integrative role in the nociceptive transmission process under inflammatory conditions. In the present study, behavioural and in vivo electrophysiological methods were used to examine the peripheral role of P2 receptors in the persistent nociceptive responses induced by subcutaneous bee venom injection (2 mg/mL) in. Sprague-Dawley rats Local pretreatment with the wide-spectrum P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 1 mmol/L, 50 μL) 10 min prior to s.c. bee venom injection significantly suppressed the duration of spontaneous nociceptive lifting/licking behaviour, inhibited mechanical hyperalgesia and decreased the firing of spinal dorsal horn wide dynamic range neurons in response to bee venom, without affecting primary thermal and mirror-image hyperalgesia. The localized antinociceptive action of PPADS was not due to a systemic effect, because application of the same dose of PPADS to the contralateral side was not effective. The results suggest that activation of peripheral P2 receptors is involved in the induction of nociceptive responses, mechanical hyperalgesia and the excitation of sensory spinal neurons.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Role of peripheral purinoceptors in the development of bee venom‐induced nociception: A behavioural and electrophysiological study in rats

Luo

Fan

et al. 2014

Clin Exp Pharma Physio

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“…Other data from the literature suggest the role of PPADS in antinociception. The intraperitoneal administration of PPADS after chronic constriction injury of the sciatic nerve inhibits both thermal hyperalgesia and mechanical allodynia (Borsani et al, 2008; Martucci et al, 2008), and intrathecal pretreatment significantly suppresses both the first and the second phase of FORM‐related behavior (Tsuda et al, 1999). Moreover, because both phases of FORM‐evoked nociceptive behaviors were potentiated by a selective allosteric enhancer of P2X 3 receptor function (Jarvis et al, 2002), the involvement of P2X 3 receptors in acute and inflammatory pain is very likely.…”

Section: Discussionmentioning

confidence: 99%

Peripheral purinergic receptor modulation influences the trigeminal ganglia nitroxidergic system in an experimental murine model of inflammatory orofacial pain

Borsani

Albertini

Labanca

et al. 2010

J of Neuroscience Research

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ATP plays an important role as an endogenous pain mediator generating and/or modulating pain signaling from the periphery to the central nervous system. The aim of this study was to analyze the role of peripheral purinergic receptors in modulation of the nitroxidergic system at a trigeminal ganglia level by monitoring changes in nitric oxide synthase isoforms. We also evaluated Fos-positive neurons in brainstem (spinal trigeminal nucleus) and pain-related behavior. We found that local administration of the P2 purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) decreased face-rubbing activity, nitric oxide synthase isoform expression in trigeminal ganglia, and Fos expression in spinal trigeminal nucleus after subcutaneous injection of formalin. These results suggest a role for peripheral P2 purinergic receptors in orofacial pain transmission through modulation of the nitroxidergic system. .

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“…Such requirements could be addressed by new information on the neuronal mechanisms of this pathology. The availability of animal models for this condition has permitted us to observe related morphological and molecular alteration in both the central, [ 1 , 2 , 3 ] and the peripheral nervous systems [ 2 , 4 , 5 , 6 ]. Moreover, a link between the impairment of the nervous system and an alteration of skin homeostasis (morphology and expression of molecular markers involved in nociception) has been demonstrated during neuropathic pathologies [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Single Administration of Melatonin Modulates the Nitroxidergic System at the Peripheral Level and Reduces Thermal Nociceptive Hypersensitivity in Neuropathic Rats

Borsani

Buffoli

Bonazza

et al. 2017

IJMS

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Neuropathic pain is a severe condition with unsatisfactory treatments. Melatonin, an indolamine, seems to be a promising molecule suitable for this purpose due to its well-known anti-inflammatory, analgesic, and antioxidant effects, as well as its modulation of the nitroxidergic system. Nevertheless, the data on its mechanism of action and potentialities are currently insufficient in this pathology, especially at the peripheral level. Thus, this work evaluated the effect of a single administration of melatonin in an established mononeuropathy pain model that monitors the behaviour and the changes in the nitroxidergic system in dorsal root ganglia and skin, which are affected by nervous impairment. Experiments were carried out on Sprague Dawley rats subdivided into the sham operated (control) and the chronic constriction injured animals, a model of peripheral neuropathic pain on sciatic nerve. Single administrations of melatonin (5–10 mg/kg) or vehicle were injected intraperitoneally on the 14th day after surgery, when the mononeuropathy was established. The animals were behaviourally tested for thermal hyperalgesia. The dorsal root ganglia and the plantar skin of the hind-paws were removed and processed for the immunohistochemical detection of neuronal and inducible nitric oxide synthases. The behavioural results showed an increase of withdrawal latency during the plantar test as early as 30 min after melatonin administration. The immunohistochemical results indicated a modulation of the nitroxidergic system both at dorsal root ganglia and skin level, permitting speculate on a possible mechanism of action. We showed that melatonin may be a possible therapeutic strategy in neuropathic pain.

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PPADS, a purinergic antagonist reduces Fos expression at spinal cord level in a mouse model of mononeuropathy

Cited by 9 publications

References 56 publications

Role of peripheral purinoceptors in the development of bee venom‐induced nociception: A behavioural and electrophysiological study in rats

Role of peripheral purinoceptors in the development of bee venom‐induced nociception: A behavioural and electrophysiological study in rats

Peripheral purinergic receptor modulation influences the trigeminal ganglia nitroxidergic system in an experimental murine model of inflammatory orofacial pain

Single Administration of Melatonin Modulates the Nitroxidergic System at the Peripheral Level and Reduces Thermal Nociceptive Hypersensitivity in Neuropathic Rats

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