The Opiorphin Analog STR-324 Decreases Sensory Hypersensitivity in a Rat Model of Neuropathic Pain.
Anesth Analg
; 126(6): 2102-2111, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-28806211
ABSTRACT
BACKGROUND:
Neuropathic pain represents a therapeutic challenge, and treatments with increased efficacy and tolerability still need to be developed. Opiorphin protects endogenous enkephalins from degradation, potentiating enkephalin-dependent analgesia via the activation of opioid pathways. Enkephalins are natural ligands of opioid receptors, with strong affinity for δ-opioid receptors. Expression of functional δ-opioid receptors increases in sensory neurons after peripheral nerve injury in neuropathic pain models. In a postoperative pain model, opiorphin and its stable analog STR-324 have an analgesic potency comparable to that of morphine, but without adverse opioid-related side effects. Consequently, administration of endogenous opiorphin peptides or STR-324 might be effective in managing peripheral neuropathic pain.METHODS:
In this study, STR-324 was administered intravenously over the course of 7 days to rats with mononeuropathy induced by L5-L6 spinal nerve root ligation. The rats exhibited mechanical allodynia, thermal hyperalgesia, and spontaneous pain-related behavior throughout the testing period.RESULTS:
Here, we report that the continuous administration of STR-324 significantly reduced mechanical allodynia and spontaneous pain-related behavior from day 2 to day 7 in animals that received 10 or 50 µg/h of STR-324 as compared to placebo-treated animals (P < .00001 and P < .0011, respectively, for mechanical allodynia; P = .028 and P = .0049, respectively, for spontaneous pain-related behavior). In addition, STR-324 reduced the pain-evoked expression of spinal c-Fos in this model, demonstrating that it acts at least in part through inhibition of endogenous nociceptive pathways.CONCLUSIONS:
These observations suggested that STR-324 may be an effective addition to the multimodal approach for treating clinical neuropathic pain.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Proteínas e Peptídeos Salivares
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Medição da Dor
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Modelos Animais de Doenças
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Hiperalgesia
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Neuralgia
Limite:
Animals
Idioma:
En
Revista:
Anesth Analg
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França