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Simultaneous targeting of MOR/DOR: A useful strategy for inflammatory pain modulation
- Source :
- European Journal of Pharmacology. 847:97-102
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Development of new analgesics endowed with mu/delta opioid receptor (MOR/DOR) activity represents a promising alternative to MOR selective compounds because of their better therapeutic and tolerability profile. Lately, we have synthetized the MOR/DOR agonist LP2 that showed a long lasting antinociceptive activity in the tail flick test, an acute pain model. Here, we investigate whether LP2 is also effective in the mouse formalin test, a model of inflammatory pain sustained by mechanisms of central sensitization. Moreover, we evaluated a possible peripheral component of LP2 analgesic activity. Different doses of LP2 were tested after either intraperitoneal (i.p.) or intraplantar (i.pl.) administration. LP2 (0.75–1.00 mg/kg, i.p.), dose-dependently, counteracted both phases of the formalin test after i.p. administration. The analgesic activity of LP2 (0.75–1.00 mg/kg) was completely blocked by a pretreatment with the opioid antagonist naloxone (3 mg/kg, i.p.). Differently, the pretreatment with naloxone methiodide (5 mg/kg, i.p.), a peripherally restricted opioid antagonist, completely blocked the lower analgesic dose of LP2 (0.75 mg/kg) but only partially relieved the antinociceptive effects of LP2 at the dose of 1.00 mg/kg, thus revealing a peripheral analgesic component of LP2. I.pl. injections of LP2 (10–20 μg/10 μl) were also performed to investigate a possible effect of LP2 on peripheral nerve terminals. Nociceptive sensitization, which occur both at peripheral and central level, is a fundamental step for pain chronicization, thus LP2 is a promising drug for pain conditions characterized by nociceptive sensitization.
- Subjects :
- Male
0301 basic medicine
Agonist
Mouse formalin test
Multitarget ligands
Naloxone
Naloxone methiodide
Opioid
Pain
Rotarod
Pharmacology
medicine.drug_class
Narcotic Antagonists
Analgesic
Receptors, Opioid, mu
(+)-Naloxone
δ-opioid receptor
Mice
03 medical and health sciences
0302 clinical medicine
Receptors, Opioid, delta
medicine
Animals
Sensitization
Pain Measurement
Inflammation
business.industry
Analgesics, Opioid
030104 developmental biology
medicine.anatomical_structure
business
030217 neurology & neurosurgery
Tail flick test
Opioid antagonist
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 847
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....cda3c8a0d90e2afa4aada3f279769d92