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Effect of diphenylhydramine on the Tyr-MIF-1 antinociception in rats
A Bocheva1, R Zamfirova, T Pajpanova
1Institute of Physiology Bulgarian Academy of Sciences, Sofia, Bulgaria. bocheva@iph.bio.bas.bg
Abstract:
Tyr-MIF-1 is a representative of the MIF's family of endogenous peptides. It has been isolated from bovine hypothalamus and human parietal cortex that suggests its involvement in nociception. Tyr-MIF-1 can bind to the mu-receptors as well as to its specific non-opiate receptors in the brain. Data in the literature rise the idea that histamine (HA), a well known nociceptive agent, and Tyr-MIF-1 might have a common pathway in their effects on nociception. We tested that possibility by investigation of the combined action of diphenhydramine (DPH, an H (1) -antagonist) and Tyr-MIF-1 on nociception. The changes in the nociceptive effects were examined in the male Wistar rats by the Randall-Sellito paw-pressure (PP) and the tail-flick (TF) tests. Tyr-MIF-1 in a dose of 1 mg/kg exerted strong naloxone-reversible analgesic effects. DPH (100 microg/kg, i.p.) had an antinociceptive action, too. The co-administration of Tyr-MIF-1 and DPH enhanced the antinociceptive effect, as compared to DPH (PP) and to TYR-MIF-1 alone (TF). These effects were reversed when methylene blue (MB, 500 microg/rat) was applied 1h before the combination. However, naloxone (1 mg/kg, i.p.) only slightly affected the antinociceptive effect of DPH and TYR-MIF-1, compared to that of MB. The results obtained confirmed the hypothesis that cyclic nucleotides are involved in the realization of nociceptive effects of both HA and Tyr-MIF-1.
Insights
The study investigated the pain-relieving effects of Tyr-MIF-1 and diphenhydramine (DPH), finding their combined action enhances pain reduction. This suggests a common pathway involving cyclic nucleotides for both histamine and Tyr-MIF-1 in pain perception.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Tyr-MIF-1, an endogenous peptide found in the hypothalamus and cortex, is implicated in pain perception.
- Histamine (HA) is a known pain-inducing agent, and preliminary data suggest a shared pathway with Tyr-MIF-1.
Purpose of the Study:
- To investigate the potential common pathway between histamine and Tyr-MIF-1 in nociception.
- To examine the combined effects of diphenhydramine (DPH), an H(1)-antagonist, and Tyr-MIF-1 on pain responses in rats.
Main Methods:
- Male Wistar rats were used to assess nociception via Randall-Sellito paw-pressure (PP) and tail-flick (TF) tests.
- The study evaluated the effects of Tyr-MIF-1, DPH, and their co-administration, along with naloxone and methylene blue (MB).
Main Results:
- Tyr-MIF-1 (1 mg/kg) demonstrated significant naloxone-reversible analgesic effects.
- DPH (100 microg/kg) also exhibited antinociceptive properties.
- Co-administration of Tyr-MIF-1 and DPH resulted in enhanced antinociception compared to individual treatments.
- Methylene blue reversed these combined effects, while naloxone had a minimal impact.
Conclusions:
- The findings support the hypothesis that Tyr-MIF-1 and histamine share a common pathway in modulating nociception.
- Cyclic nucleotides are likely involved in mediating the nociceptive effects of both histamine and Tyr-MIF-1.