Cytokine inhibitors and pain control

Context: Various parts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) have been used in Ghanaian and African traditional medicine as an analgesic. However, there are little scientific data to support the anti-nociceptive effects of the hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) as well as the possible mechanisms involved in its anti-nociceptive effects. Purpose: To predict possible nociceptive pathways involved in the anti-nociceptive effects of EthE. Materials and methods: The effect of EthE (30, 100 and 300 mg/kg) on intraplantar injection of pain mediators such as interleukin-1b, tumour necrosis factor-a, prostaglandin E 2 and bradykinin was evaluated in male Sprague Dawley rats using Randall-Selitto test for 5 h. The effect of specific antagonists to the opioidergic, adenosinergic, ATP-sensitive K þ channels, nitric oxide, serotonergic, muscarinic, adrenergic and voltage-gated calcium channel on the anti-nociceptive effect of EthE (100 mg/kg) was evaluated using the formalin test in male imprinting control region (ICR) mice for 1 h. Results: Pretreatment of the rats with EthE significantly reversed the hypernociception induced by intraplantar injection of TNF-a (F 4,120 ¼ 10.86, p < 0.0001), IL-1b (F 4,120 ¼ 14.71, p < 0.0001), bradykinin (F 4,80 ¼ 12.52, p < 0.0001) and prostaglandin E 2 (F 5,144 ¼ 6.165, p ¼ 0.0001). The anti-nociceptive effect exhibited by EthE in the formalin test was reversed by systemic administration of N G -L-nitro-arginine methyl ester, naloxone, theophylline and glibenclamide. Conclusions: EthE inhibits hypernociception induced by TNF-a, IL-1b, bradykinin and prostaglandin E 2 . EthE exhibited anti-nociceptive effects possibly mediated through opioidergic, adenosinergic, ATP-sensitive potassium channels and nitric oxide cyclic GMP pathways. ARTICLE HISTORY

Section: Discussionmentioning

confidence: 99%

Possible mechanisms involved in the anti-nociceptive effects of hydro-ethanolic leaf extract ofZiziphus abyssinica

Boakye‐Gyasi

Henneh

Abotsi

et al. 2017

“…Intraplantar injection of CG is largely known to produce inflammation and nociception through a cytokine cascade released by resident or migrating cells, mainly initiated by production of bradykinin (Verri et al, 2007). This cascade of signalization is believed to lead to the release of prostanoids and sympathomimetic amines (Cunha et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Citronellal, a monoterpene present in Java citronella oil, attenuates mechanical nociception response in mice

Santana

Oliveira

Santana

et al. 2013

Context: Citronellal is a monoterpene present in the oil of many species, including Cymbopogon winterianus Jowitt (Poaceae).Objective: The present study investigated the effect of citronellal on inflammatory nociception induced by different stimuli and examined the involvement of the NO-cGMP-ATP-sensitive K þ channel pathway. Materials and methods: We used male Swiss mice (n ¼ 6 per group) that were treated intraperitoneally with citronellal (25, 50 or 100 mg/kg) 0.5 h after the subplantar injection of 20 ml of carrageenan (CG; 300 mg/paw), tumor necrosis factor-a (TNF-a; 100 pg/paw), prostaglandin E 2 (PGE 2 ; 100 ng/paw) or dopamine (DA; 30 mg/paw). The mechanical nociception was evaluated at 0.5, 1, 2 and 3 h after the injection of the agents, using a digital analgesimeter (von Frey). The effects of citronellal were also evaluated in the presence of L-NAME (30 mg/kg) or glibenclamide (5 mg/kg). Results: At all times, citronellal in all doses inhibited the development of mechanical nociception induced by CG (p50.001 and p50.01) and TNF-a (p50.001, p50.01, and p50.05). The citronellal was able to increase the pain threshold in the DA test (p50.001, p50.01, and p50.05) and in the PGE 2 test at all times (p50.001 and p50.05). L-NAME and glibenclamide reversed the antinociceptive effects of the citronellal at higher doses in the PGE 2 test. Discussion and conclusion: These data suggest that citronellal attenuated mechanical nociception, mediated in part by the NO-cGMP-ATP-sensitive K þ channel pathway.

“…This is an important mechanism since hyperalgesic cytokines such as tumor necrosis factor a (TNFa) and interleukin (IL)-1b are crucial mediators in pain (Cunha et al, 2005(Cunha et al, , 2010b. Their nociceptive effect is consistent in models of overt pain-like behavior, and thermal and mechanical hyperalgesia suggesting that targeting nociceptive cytokines has potential therapeutic application (Verri et al, 2006a(Verri et al, , 2007a. Despite the presence of flavonoids in plants of Tephosia genus and the known effects and mechanisms of flavonoids, no study assessed the analgesic effect of Tephrosia genus plants.…”

Section: Introductionmentioning

confidence: 99%

Tephrosia sinapouethyl acetate extract inhibits inflammatory pain in mice: Opioid receptor dependent inhibition of TNFαand IL-1βproduction

Martínez¹,

Zarpelon²,

Cardoso³

et al. 2013

Context: Tephrosia toxicaria is currently known as Tephrosia sinapou (Buc'hoz) A. Chev. (Fabaceae) and is a source of compounds such as flavonoids that inhibit inflammatory pain. Objective: To investigate the analgesic effect and mechanisms of the ethyl acetate extract of T. sinapou in inflammatory pain in mice. Materials and methods: Behavioral responses were evaluated using mechanical (1-24 h) and thermal hyperalgesia (0.5-5 h), writhing response (20 min) and rota-rod (1-5 h) tests. Neutrophil recruitment (myeloperoxidase activity), cytokines (tumor necrosis factor [TNF]a and interleukin [IL]-1b), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels were determined by colorimetric assays. Pharmacological treatments were opioid receptor antagonist (naloxone, 0.1-1 mg/kg) and control opioid (morphine, 5 mg/kg). Inflammatory stimuli were carrageenin (100 mg/paw), complete Freund's adjuvant (CFA, 10 ml/paw), prostaglandin E 2 (PGE 2 , 100 ng/paw) and acetic acid (0.8%). Results: The intraperitoneal pre-treatment with extract inhibited in a dose-dependent (30-300 mg/kg) dependent manner the mechanical hyperalgesia induced by carrageenin (up to 93% inhibition). The post-treatment (100 mg/kg) inhibited CFA-induced hyperalgesia (up to 63% inhibition). Naloxone (1 mg/kg) prevented the inhibitory effect of the extract over carrageenin-induced mechanical (100%) and thermal (100%) hyperalgesia, neutrophil recruitment (52%) and TNFa (63%) and IL-1b (98%) production, thermal threshold in naïve mice (99%), PGE 2 -induced mechanical hyperalgesia (88%) and acetic acid-induced writhing response (49%). There was no significant alteration in the rota-rod test, and AST and ALT serum levels by extract treatment. Discussion and conclusion: Tephrosia sinapou ethyl acetate extract reduces inflammatory pain by activating an opioid receptor-dependent mechanism.