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Phα1β, a peptide from the venom of the spider Phoneutria nigriventer shows antinociceptive effects after continuous infusion in a neuropathic pain model in rats.
Anesth Analg. 2014 Jul; 119(1):196-202.A&A

Abstract

BACKGROUND

Neuropathic pain is a severe painful pathology that is difficult to treat. One option for its management is the continuous intrathecal (i.t.) infusion of ziconotide (the Conus magnus peptide ω-conotoxin MVIIA), which, in addition to being effective, produces serious adverse effects at analgesic doses. Single i.t. administration of Phα1β, a peptide purified from the venom of the spider Phoneutria nigriventer, has antinociceptive effects with a greater therapeutic window than ziconotide in rodents. To further evaluate its analgesic potential, we investigated the antinociceptive and toxic effects of Phα1β after single or continuous i.t. infusion in a rat model of neuropathic pain.

METHODS

Adult male Wistar rats (200-300 g) bred in-house were used. Chronic constriction injury (CCI) of the sciatic nerve was used as the neuropathic pain model. Nociception was assessed by detecting mechanical hyperalgesia, considering a significant reduction in 50% paw withdrawal threshold values after CCI compared with baseline values. First, we assessed the antinociceptive effect of a single i.t. injection of Phα1β (10, 30, or 100 pmol/site) in a model of neuropathic pain 8 days after nerve injury. In a different experiment, we delivered Phα1β (60 pmol/μL/h) or vehicle (phosphate-buffered saline, 1.0 μL/h) through continuous infusion using an osmotic pump by spinal catheterization for 7 days in rats submitted to nerve injury. Behavioral adverse effects were evaluated after single or continuous Phα1β i.t. administration, and histopathological analysis of spinal cord, brainstem, and encephalon was performed after continuous Phα1β i.t. injection.

RESULTS

We observed that CCI of the sciatic nerve but not sham surgery caused intense (reduction of approximately 2.5 times in mechanical withdrawal threshold) and persistent (up to 14 days) nociception in rats. The single i.t. injection of Phα1β (30 or 100 pmol/site) reduced neuropathic nociception from 1 to 6 hours after administration, without showing detectable side effects. Similarly, the continuous infusion of Phα1β (60 pmol/μL/h for 7 days) was also able to reverse nerve injury-induced nociception from 1 to 7 days, but did not cause either behavioral side effects or histopathological changes in the central nervous system.

CONCLUSIONS

Thus, we have shown for the first time that the continuous i.t. delivery of Phα1β produces analgesia disconnected from toxicity in a relevant model of neuropathic pain, indicating that it is an effective and safe drug with a great potential to treat pain.

Authors+Show Affiliations

From the *Graduate Program in Biological Sciences: Toxicological Biochemistry, Department of Chemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria (UFSM), Santa Maria (RS); †Laboratory of Molecular and Cellular Biology, Graduate Program of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil; ‡Graduate Program in Health Sciences: Medicine and Biomedicine, Institute of Education and Research, Santa Casa de Belo Horizonte, Grupo Santa Casa de Belo Horizonte, Belo Horizonte (MG), Brazil; §Department of Pharmacology, Biological Sciences Centre, Federal University of Santa Catarina, Florianópolis, Santa Catarina; and ¶Ezequiel Dias Foundation, Belo Horizonte (MG), Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24836473

Citation

Rosa, Fernanda, et al. "Phα1β, a Peptide From the Venom of the Spider Phoneutria Nigriventer Shows Antinociceptive Effects After Continuous Infusion in a Neuropathic Pain Model in Rats." Anesthesia and Analgesia, vol. 119, no. 1, 2014, pp. 196-202.
Rosa F, Trevisan G, Rigo FK, et al. Phα1β, a peptide from the venom of the spider Phoneutria nigriventer shows antinociceptive effects after continuous infusion in a neuropathic pain model in rats. Anesth Analg. 2014;119(1):196-202.
Rosa, F., Trevisan, G., Rigo, F. K., Tonello, R., Andrade, E. L., Cordeiro, M. d. o. . N., Calixto, J. B., Gomez, M. V., & Ferreira, J. (2014). Phα1β, a peptide from the venom of the spider Phoneutria nigriventer shows antinociceptive effects after continuous infusion in a neuropathic pain model in rats. Anesthesia and Analgesia, 119(1), 196-202. https://doi.org/10.1213/ANE.0000000000000249
Rosa F, et al. Phα1β, a Peptide From the Venom of the Spider Phoneutria Nigriventer Shows Antinociceptive Effects After Continuous Infusion in a Neuropathic Pain Model in Rats. Anesth Analg. 2014;119(1):196-202. PubMed PMID: 24836473.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phα1β, a peptide from the venom of the spider Phoneutria nigriventer shows antinociceptive effects after continuous infusion in a neuropathic pain model in rats. AU - Rosa,Fernanda, AU - Trevisan,Gabriela, AU - Rigo,Flávia Karine, AU - Tonello,Raquel, AU - Andrade,Edinéia Lemos, AU - Cordeiro,Marta do Nascimento, AU - Calixto,João Batista, AU - Gomez,Marcus Vinícius, AU - Ferreira,Juliano, PY - 2014/5/20/entrez PY - 2014/5/20/pubmed PY - 2014/8/20/medline SP - 196 EP - 202 JF - Anesthesia and analgesia JO - Anesth Analg VL - 119 IS - 1 N2 - BACKGROUND: Neuropathic pain is a severe painful pathology that is difficult to treat. One option for its management is the continuous intrathecal (i.t.) infusion of ziconotide (the Conus magnus peptide ω-conotoxin MVIIA), which, in addition to being effective, produces serious adverse effects at analgesic doses. Single i.t. administration of Phα1β, a peptide purified from the venom of the spider Phoneutria nigriventer, has antinociceptive effects with a greater therapeutic window than ziconotide in rodents. To further evaluate its analgesic potential, we investigated the antinociceptive and toxic effects of Phα1β after single or continuous i.t. infusion in a rat model of neuropathic pain. METHODS: Adult male Wistar rats (200-300 g) bred in-house were used. Chronic constriction injury (CCI) of the sciatic nerve was used as the neuropathic pain model. Nociception was assessed by detecting mechanical hyperalgesia, considering a significant reduction in 50% paw withdrawal threshold values after CCI compared with baseline values. First, we assessed the antinociceptive effect of a single i.t. injection of Phα1β (10, 30, or 100 pmol/site) in a model of neuropathic pain 8 days after nerve injury. In a different experiment, we delivered Phα1β (60 pmol/μL/h) or vehicle (phosphate-buffered saline, 1.0 μL/h) through continuous infusion using an osmotic pump by spinal catheterization for 7 days in rats submitted to nerve injury. Behavioral adverse effects were evaluated after single or continuous Phα1β i.t. administration, and histopathological analysis of spinal cord, brainstem, and encephalon was performed after continuous Phα1β i.t. injection. RESULTS: We observed that CCI of the sciatic nerve but not sham surgery caused intense (reduction of approximately 2.5 times in mechanical withdrawal threshold) and persistent (up to 14 days) nociception in rats. The single i.t. injection of Phα1β (30 or 100 pmol/site) reduced neuropathic nociception from 1 to 6 hours after administration, without showing detectable side effects. Similarly, the continuous infusion of Phα1β (60 pmol/μL/h for 7 days) was also able to reverse nerve injury-induced nociception from 1 to 7 days, but did not cause either behavioral side effects or histopathological changes in the central nervous system. CONCLUSIONS: Thus, we have shown for the first time that the continuous i.t. delivery of Phα1β produces analgesia disconnected from toxicity in a relevant model of neuropathic pain, indicating that it is an effective and safe drug with a great potential to treat pain. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/24836473/Phα1β_a_peptide_from_the_venom_of_the_spider_Phoneutria_nigriventer_shows_antinociceptive_effects_after_continuous_infusion_in_a_neuropathic_pain_model_in_rats_ L2 - https://doi.org/10.1213/ANE.0000000000000249 DB - PRIME DP - Unbound Medicine ER -