Efficacy of 2-Hydroxyflavanone in Rodent Models of Pain and Inflammation: Involvement of Opioidergic and GABAergic Anti-Nociceptive Mechanisms

Molecules. 2022 Aug 25;27(17):5431. doi: 10.3390/molecules27175431.

Abstract

The current work examined the pharmacological potential of a selected flavanone derivative 2-hydroxyflavanone as a promising remedy for the treatment and management of pain. The selected flavanone derivative (2-HF) was evaluated for its analgesic and anti-inflammatory potentials following standard pharmacological protocols including hot plate, acetic acid-induced writhing and tail immersion tests. Naloxone and pentylenetetrazol were used to evaluate the potential implication of GABAergic and opioidergic mechanisms. The anti-inflammatory potential of 2-HF was confirmed using carrageenan-, serotonin- and histamine-induced paw edema models as well as a xylene-induced ear edema model. Furthermore, the anti-neuropathic potential of 2-HF was tested using a cisplatin-induced neuropathic pain model. Our sample, at the tested concentrations of 15, 30 and 45 mg kg-1, showed considerable analgesic, anti-inflammatory effects, as well as efficacy against neuropathic pain. Naloxone and pentylenetetrazol at 1 and 15 mg kg-1 antagonized the anti-nociceptive activities of 2-hydroxyflavanone indicating the involvement of opioidergic and GABAergic mechanisms. In the static allodynia model, combination of gabapentin 75 mg kg-1 with 2-HF at 15, 30, 45 mg kg-1 doses exhibited considerable efficacy. In cold allodynia, 2-hydroxyflavanone, at doses of 15, 30 and 45 mg kg-1 and in combination with gabapentin (75 mg kg-1), demonstrated prominent anti-allodynic effects. The paw withdrawal latency was considerably increased in gabapentin + cisplatin treated groups. Moreover, cisplatin + 2-hydroxyflavanone 15, 30, 45 mg kg-1 showed increases in paw withdrawal latency. Likewise, considerable efficacy was observed for 2-hydroxyflavanone in thermal hyperalgesia and dynamic allodynia models. Our findings suggest that 2-hydroxyflavanone is a potential remedy for pain syndrome, possibly mediated through opioidergic and GABAergic mechanisms.

Keywords: GABAergic mechanisms; allodynia; analgesia; hyperalgesia; neuropathy.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Cisplatin / adverse effects
  • Disease Models, Animal
  • Edema / chemically induced
  • Edema / drug therapy
  • Flavanones* / therapeutic use
  • Gabapentin / pharmacology
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Inflammation / drug therapy
  • Naloxone / pharmacology
  • Naloxone / therapeutic use
  • Neuralgia* / chemically induced
  • Neuralgia* / drug therapy
  • Pentylenetetrazole / adverse effects
  • Rodentia

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Flavanones
  • Naloxone
  • Gabapentin
  • Cisplatin
  • Pentylenetetrazole

Grants and funding

This research received no external funding.