The effects of opioids and NMDA receptor antagonists on the body temperature and acute nociceptive pain in rats

Uvod: Pored antinocicepcije, opioidi ispoljavaju značajne efekte i na telesnu temperaturu. Brojni dokazi podržavaju postojanje endogenog glutamatergičkog sistema koji moduliše telesnu temperaturu preko N-metil-D-aspartat (NMDA) receptora. Ketamin i magnezijum, NMDA antagonisti, su poznati po svojim anestetičkim, anagletičkim svojstvima, kao i dejstvu protiv drhtavice. Takođe, oni mogu povećati antinociceptivne efekte opioidnih analgetika u različitim modelima bola kod životinja, kao i kod ljudi. Cilj ispitivanja: Cilj ovog ispitivanja bilo je poređenje antinociceptivnih i hipertermnih odgovora između dve grupe agonista μ-opioidnih receptora: derivata fentanila (4-anilinopiperidinski tip) i morfina (fenantrenski tip) kod pacova. Takođe, ova studija imala je za cilj ispitivanje efekata ketamina i magnezijum sulfata na telesnu temperaturu i akutni nociceptivni bol kod pacova, da utvrdi tip interakcije između ova dva leka i da ispita da li magnezijum sulfat dodat ketaminu ili kombinaciji morfin-ketamin, povećava analgetički efekt ovih lekova i njihov efekt na telesnu temperaturu. Metode: Analgetička aktivnosti procenjivana je testom potapanja repa mužjaka Wistar pacova (200-250 g) u toplu vodu. Distalnih 5 cm repa stavljano je u toplu vodu (55 ± 0,5°C) i kao odgovor mereno je vreme za koje životinja povuče rep iz tople vode. Telesna temperatura je merena stavljanjem termometarske sonde u dužini od 5 cm u debelo crevo. Rezultati: Fentanil, (±)-cis-3-metil fentanil (CM), (±)-cis-3-karbometoksi fentanil, (±)- trans-3-karbometoksi fentanil i (±)-cis-3-butil- fentanil, kao i morfin, oksikodon (O), tebakon i 6,14-etenomorfinan-7-metanol, 4,5-epoksi-6-fluoro-3-hidroksi-,,17-trimetil-, (5,7) izazivali su dozno-zavisno povećanje antinocicepcije i hipertermije. Derivati morfina (fenantrenski tip) i fentanila (4-anilinopiperidinski tip) izazivali su hipertermiju kod pacova u dozama koje su oko 2 puta niže i 6-11 puta više od njihovih srednjih antinociceptivnih doza...Introduction: In addition to producing antinociception, opioids exert profound effects on body temperature. A large body of evidence supports the existence of an endogenous glutamate system that tonically modulates body temperature viaN-methyl-D-aspartate (NMDA) receptors. Ketamine and magnesium, both NMDA receptor antagonists, are known for their anesthetic, analgesic and anti-shivering properties. They also enhance the antinociceptive effects of opioid analgesics in different animal models of pain, as well as in humans. Aim: This study aimed at comparing antinociceptive and hyperthermic responses between two groups of μ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Also, study is aimed at evaluating the effects of ketamine and magnesium sulphate on body temperature and acute nociceptive pain in rats, to determine the type of interaction between them and at evaluating whether magnesium sulfate added to ketamine or morphine-ketamine combination produces higher level of analgesia and higher effect on body temperature. Methods: Analgesic activity was assessed by tail-immersion test in male Wistar rats (200- 250 g). The distal 5 cm of the tail was immersed in a warm water bath (55 0.5°C) and the time for tail-withdrawal was measured as a response latency. The body temperature was measured by insertion of a thermometer probe 5 cm into the colon of unrestrained rats. Results: Fentanyl, ()cis-3-methyl fentanyl, ()cis-3-carbomethoxy fentanyl, ()trans-3- carbomethoxy fentanyl and ()cis-3 butyl fentanyl and morphine, oxycodone, thebacon and 6,14-Ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-,,17-trimethyl- , (5,7)produced dose-dependent increase in antinociception and hyperthermia. Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6 to 11 times higher, than their median antinociceptive doses..

The effects of opioids and NMDA receptor antagonists on the body temperature and acute nociceptive pain in rats

Uvod: Pored antinocicepcije, opioidi ispoljavaju značajne efekte i na telesnu temperaturu. Brojni dokazi podržavaju postojanje endogenog glutamatergičkog sistema koji moduliše telesnu temperaturu preko N-metil-D-aspartat (NMDA) receptora. Ketamin i magnezijum, NMDA antagonisti, su poznati po svojim anestetičkim, anagletičkim svojstvima, kao i dejstvu protiv drhtavice. Takođe, oni mogu povećati antinociceptivne efekte opioidnih analgetika u različitim modelima bola kod životinja, kao i kod ljudi. Cilj ispitivanja: Cilj ovog ispitivanja bilo je poređenje antinociceptivnih i hipertermnih odgovora između dve grupe agonista μ-opioidnih receptora: derivata fentanila (4-anilinopiperidinski tip) i morfina (fenantrenski tip) kod pacova. Takođe, ova studija imala je za cilj ispitivanje efekata ketamina i magnezijum sulfata na telesnu temperaturu i akutni nociceptivni bol kod pacova, da utvrdi tip interakcije između ova dva leka i da ispita da li magnezijum sulfat dodat ketaminu ili kombinaciji morfin-ketamin, povećava analgetički efekt ovih lekova i njihov efekt na telesnu temperaturu. Metode: Analgetička aktivnosti procenjivana je testom potapanja repa mužjaka Wistar pacova (200-250 g) u toplu vodu. Distalnih 5 cm repa stavljano je u toplu vodu (55 ± 0,5°C) i kao odgovor mereno je vreme za koje životinja povuče rep iz tople vode. Telesna temperatura je merena stavljanjem termometarske sonde u dužini od 5 cm u debelo crevo. Rezultati: Fentanil, (±)-cis-3-metil fentanil (CM), (±)-cis-3-karbometoksi fentanil, (±)- trans-3-karbometoksi fentanil i (±)-cis-3-butil- fentanil, kao i morfin, oksikodon (O), tebakon i 6,14-etenomorfinan-7-metanol, 4,5-epoksi-6-fluoro-3-hidroksi-,,17-trimetil-, (5,7) izazivali su dozno-zavisno povećanje antinocicepcije i hipertermije. Derivati morfina (fenantrenski tip) i fentanila (4-anilinopiperidinski tip) izazivali su hipertermiju kod pacova u dozama koje su oko 2 puta niže i 6-11 puta više od njihovih srednjih antinociceptivnih doza...Introduction: In addition to producing antinociception, opioids exert profound effects on body temperature. A large body of evidence supports the existence of an endogenous glutamate system that tonically modulates body temperature viaN-methyl-D-aspartate (NMDA) receptors. Ketamine and magnesium, both NMDA receptor antagonists, are known for their anesthetic, analgesic and anti-shivering properties. They also enhance the antinociceptive effects of opioid analgesics in different animal models of pain, as well as in humans. Aim: This study aimed at comparing antinociceptive and hyperthermic responses between two groups of μ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Also, study is aimed at evaluating the effects of ketamine and magnesium sulphate on body temperature and acute nociceptive pain in rats, to determine the type of interaction between them and at evaluating whether magnesium sulfate added to ketamine or morphine-ketamine combination produces higher level of analgesia and higher effect on body temperature. Methods: Analgesic activity was assessed by tail-immersion test in male Wistar rats (200- 250 g). The distal 5 cm of the tail was immersed in a warm water bath (55 0.5°C) and the time for tail-withdrawal was measured as a response latency. The body temperature was measured by insertion of a thermometer probe 5 cm into the colon of unrestrained rats. Results: Fentanyl, ()cis-3-methyl fentanyl, ()cis-3-carbomethoxy fentanyl, ()trans-3- carbomethoxy fentanyl and ()cis-3 butyl fentanyl and morphine, oxycodone, thebacon and 6,14-Ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-,,17-trimethyl- , (5,7)produced dose-dependent increase in antinociception and hyperthermia. Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6 to 11 times higher, than their median antinociceptive doses..

Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels

Background: In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. Methods: Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum. Results: Magnesium sulfate administered subcutaneously (0.005-45 mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45 mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity. Conclusions: Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency