Investigation of possible interactions of pain modification actions of endogenous enkephalinergic and noradrenergic systems in Zymosan-induced chronic inflammatory pain model


AYAR A. , KURT A. , Canpolat S.

FEPS 2014, Budapeşte, Hungary, 27 - 30 August 2014, vol.211, no.697, pp.12

  • Publication Type: Conference Paper / Summary Text
  • Volume: 211
  • City: Budapeşte
  • Country: Hungary
  • Page Numbers: pp.12

Abstract

Investigation of possible interactions of pain 
modification actions of endogenous 
enkephalinergic and noradrenergic systems in 
Zymosan-induced chronic inflammatory pain 
model
A. Ayar, A. Kurt, S. Canpolat
Department of Physiology, Karadeniz Technical University, Faculty of 
Medicine, Trabzon-Turkey
Chronic inflammatory pain, a nociceptive process associated with 
tissue damage due to inflammation mediated by increased sensitivity 
of nociceptive-specific neurons, is a feature of a large number of 
painful conditions for which no satisfactory treatment has been 
available yet. The aim of this study was to assess the possible 
analgesic affects of opiorphin, an endogenous enkephalinase 
inhibitior, and noradrenalin, known to be involved in the intrinsic 
modulation of nociceptive transmission, on inflammatory pain in rats. 
Timing the delay for the first hind paw lift to a focused thermal 
radiant heat, in vivo nociceptive behavioral "plantar test" was used for 
assessing pain sensitivity of adult male Spraque Dawley rats. After 
obtaining control nociceptive latency values, chronic inflammatory 
pain was induced by intraplantar injection of zymosan (6 mg in 200 
uL) and heat stimulated nociceptive tests were repeated. Pain 
threshold values were determined and analyzed by a pairwise 
comparison between vehicle and each opiorphin treated group using a 
Dunnett's t-test on the ranked data. Zymosan caused a persistent 
significant increase in pain sensitivity as measured 15-180 minutes 
after its intraplantar injection (P <0.05). Systemic administration of 
opiorphin (0.1-0.3 mg/kg) provided a dose dependent (P >0.05 for 0.1 
mg/kg opiorphin while P <0.05 for 0.3 mg/kg i.p opiorfin at 30 and 
40th min) inhibition of inflammatory pain. Combination of opiorphin 
with noradrenalin (1 mg/kg) provided a limited synergic action, and 
this effect was reversible by alpha-1 adrenergic blockage (prazosin 1 
mg/kg). Results from this study provides some degree of overlap 
between endogenous enkephalinergic and noradrenergic analgesic 
modification which implicates potential for development of 
therapeutical strategies involving combined use of enkephalinase 
inhibitors and noradrenergic agonists for the management of persistent 
pain associated with inflammatory painful conditions. " tabindex="" 
maxlength="2200" onkeyup="charcheck()" style="height: 
326px;width: 820px;" >0.05 for 0.1 mg/kg opiorphin while P <0.05 
for 0.3 mg/kg i.p opiorfin at 30 and 40th min) inhibition of 
inflammatory pain. Combination of opiorphin with noradrenalin (1 
mg/kg) provided a limited synergic action, and this effect was 
reversible by alpha-1 adrenergic blockage (prazosin 1 mg/kg). Results 
from this study provides some degree of overlap between endogenous 
enkephalinergic and noradrenergic analgesic modification which 
implicates potential for development of therapeutical strategies 
involving combined use of enkephalinase inhibitors and noradrenergic 
agonists for the management of persistent pain associated with 
inflammatory painful conditions. " tabindex="" maxlength="2200" 
onkeyup="charcheck()" style="height: 326px;width: 820px;" 
>Chronic inflammatory pain, a nociceptive process associated with 
tissue damage due to inflammation mediated by increased sensitivity 
of nociceptive-specific neurons, is a feature of a large number of 
painful conditions for which no satisfactory treatment has been 
available yet. The aim of this study was to assess the possible 
analgesic affects of opiorphin, an endogenous enkephalinase 
inhibitior, and noradrenalin, known to be involved in the intrinsic 
modulation of nociceptive transmission, on inflammatory pain in rats. 
Timing the delay for the first hind paw lift to a focused thermal 
radiant heat, in vivo nociceptive behavioral "plantar test" was used for 
assessing pain sensitivity of adult male Spraque Dawley rats. After 
obtaining control nociceptive latency values, chronic inflammatory 
pain was induced by intraplantar injection of zymosan (6 mg in 200 
uL) and heat stimulated nociceptive tests were repeated. Pain 
threshold values were determined and analyzed by a pairwise 
comparison between vehicle and each opiorphin treated group using a 
Dunnett's t-test on the ranked data. Zymosan caused a persistent 
significant increase in pain sensitivity as measured 15-180 minutes 
after its intraplantar injection (P <0.05). Systemic administration of 
opiorphin (0.1-0.3 mg/kg) provided a dose dependent (P >0.05 for 0.1 
mg/kg opiorphin while P <0.05 for 0.3 mg/kg i.p opiorfin at 30 and 
40th min) inhibition of inflammatory pain. Combination of opiorphin 
with noradrenalin (1 mg/kg) provided a limited synergic action, and 
this effect was reversible by alpha-1 adrenergic blockage (prazosin 1 
mg/kg). Results from this study provides some degree of overlap 
between endogenous enkephalinergic and noradrenergic analgesic 
modification which implicates potential for development of 
therapeutical strategies involving combined use of enkephalinase 
inhibitors and noradrenergic agonists for the management of persistent 
pain associated with inflammatory painful conditions.