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Pain and Analgesia: molecular mechanisms of new therapeutic drugs and targets

Dra. Yara Cury Lab de Dor Proj Dor e Analgesia

Yara Cury and Gisele Picolo


General objectives:

Pain is a health problem, affecting approximately 1 in every 5 individuals [1]. The drugs used for pain control induces health complications including addiction, tolerance and gastrointestinal bleeding and cardiac events. Thus, discovering other molecular targets which regulate pain is necessary. We aim to uncover and characterize novel molecular targets and potential therapeutic drugs for pain control. Three main themes will be pursued: 

a) Gap junction channels seem to play a role in control of nociception.

Connexins (Cx) are proteins of neuronal and glial Gap Junctions Channels (GJC), which are involved in pain causation by still poorly known mechanisms [2]. To confirm and evaluate roles of connexins in acute nociception we are using approaches in vivo (nociceptive behavioral assays and pharmacological treatments), cell culture and biochemical assays. The results might or not characterize connexins as molecular targets for pain control.

b)  Control of  toxic mitochondrial aldehyde 4-hydroxynonenal (4-HNE)- induced pain, generated during inflammatory pain process. Moreover, we develop and test novel molecules aiming to eliminate these aldehydes by activating mitochondrial enzymes. Our goal is to uncover a novel analgesic class. For this project we use nociceptive behavioral assays, biochemical and cell culture studies.

c) Novel analgesic toxins are powerful molecular tools to probe into peripheral opioid and serotonergic analgesia.

We previously reported the development of crotalphine (CRP), a structural analogue to a natural analgesic peptide first identified in the venom of the rattlesnake Crotalus durissus terrificus [3]. CRP induces potent and long lasting analgesia [4, 5], mediated by the release of endogenous opioids and activation of the cannabinoid system [6].

Another new active molecule under study in our lab is Bunodosine 391 (BDS 391), isolated from venom of the sea anemone Bunodosoma cangicum. The structural similarity between this molecule and serotonin prompted us to evaluate the possible effects of BDS 391 on this nociceptive system. Our results demonstrated that BDS 391, peripherally administered to mice and rats, induces a potent analgesic effect [7]. Thus, we intend to take advantage of BDS 391 as a molecular tool to experimentally probe into molecular mechanisms triggered by 5HT receptors.  

This experimental approach is likely to uncover molecular mechanisms in peripheral opioid and serotonergic analgesic signaling, which will be important for designing of novel and potent analgesic drugs.




1.            Goldberg, D.S. and S.J. McGee, Pain as a global public health priority. BMC Public Health. 11: p. 770.

2.            Wu, A., et al., Role of gap junctions in chronic pain. J Neurosci Res, 2012. 90(2): p. 337-45.

3.            Konno, K., et al., Crotalphine, a novel potent analgesic peptide from the venom of the South American rattlesnake Crotalus durissus terrificus. Peptides, 2008. 29(8): p. 1293-304.

4.            Gutierrez, V.P., et al., Crotalphine induces potent antinociception in neuropathic pain by acting at peripheral opioid receptors. Eur J Pharmacol, 2008. 594(1-3): p. 84-92.

5.            Zambelli, V.O., et al., Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators. Toxicon, 2008. 51(8): p. 1357-67.

6.            Machado, F.C., et al., Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine. Br J Pharmacol, 2014. 171(4): p. 961-72.

7.            Zaharenko, A.J., et al., Bunodosine 391: an analgesic acylamino acid from the venom of the sea anemone Bunodosoma cangicum. J Nat Prod, 2011. 74(3): p. 378-82.



Yara CuryPrincipal Investigator
Hugo Aguirre ArmelinPrincipal InvestigatorAssociate Investigator*(*related to this subproject)
Sandra Coccuzzo Sampaio VessoniAssociate Investigator
Gisele PicoloAssociate Investigator
Vanessa Olzon ZambelliAssociate Investigator
Daria Mochly-RosenForeign Senior Collaborator
Katsuhiro KonnoForeign Senior Collaborator
Alexandre Hiroaki KiharaSenior Collaborator
Maria Teresa Machini, Senior Collaborator
Marinilce Fagundes dos SantosSenior Collaborator
Paulo Sérgio Lacerda BeirãoSenior Collaborator
César Manuel Remuzgo RuizPostdoctoral fellow
Elisangela BressanPostdoctoral fellow
Antonio Carlos CassolaSenior Collaborator
Luciene Maria ZanchettaPostdoctoral fellow
Marucia ChacurSenior Collaborator
Rosana de Lima PaganoSenior Collaborator



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