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Termination of Nociceptive Bahaviour at the End of Phase 2 of Formalin Test is Attributable to Endogenous Inhibitory Mechanisms, but not by Opioid Receptors Activation.

Azhdari-Zarmehri H, Mohammad-Zadeh M, Feridoni M, Nazeri M - Basic Clin Neurosci (2014)

Bottom Line: While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet.While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection.While second injection of formalin, 5 minute after first injection, had no effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Sciences, Torbat heydariyeh University of Medical Sciences, Torbat heydariyeh, Iran.

ABSTRACT

Introduction: Formalin injection induces nociceptive bahaviour in phase I and II, with a quiescent phase between them. While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet. Phase II is a consequence of peripheral and central sensitization processes, which can lead to termination of the noxious stimuli responses; 45-60 minutes after formalin injection via possible recruitment of active inhibitory mechanisms which we have investigated in this study.

Methods: To test our hypothesis, in the first set of experiments, we evaluated nociceptive response after two consecutive injection of formalin (50µL, 2%), with intervals of 5 or 60 minutes. In the next set, formalin tests were carried out in companion with injection of Naloxone Hydrochloride, a non-selective antagonist of opioid receptors, pre-formalin injection and 30 and 45 minutes post formalin injection.

Results: While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection. While second injection of formalin, 5 minute after first injection, had no effect. Administration of naloxone (1mg/kg) decreased nociception in phase 2A; but had no effect on delayed termination of formalin test.

Discussion: The results of this study suggest the existence of an active inhibitory mechanism, other than the endogenous opioids, that is responsible for termination of nociceptive behaviour at the end of formalin test.

No MeSH data available.


Time scores of formalin induced nociceptive behaviours (mean ±S.E.M. of 7 or 8 rats per group) following naloxone injected minute 30 measured every 3 minutes for 90 minutes (A) and bar chart for them (B). The columns represent the mean of nociceptive score in each phase: phase 1 (1–7), interphase (8–14), phase 2A (15–60) and phase 2B (61–90), (B). Recording of the nociceptive behaviours began immediately after formalin injection (time 0) and was continued for the next 90 minutes.
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Figure 0004: Time scores of formalin induced nociceptive behaviours (mean ±S.E.M. of 7 or 8 rats per group) following naloxone injected minute 30 measured every 3 minutes for 90 minutes (A) and bar chart for them (B). The columns represent the mean of nociceptive score in each phase: phase 1 (1–7), interphase (8–14), phase 2A (15–60) and phase 2B (61–90), (B). Recording of the nociceptive behaviours began immediately after formalin injection (time 0) and was continued for the next 90 minutes.

Mentions: Naloxone (1 and 3mg/kg) administered 30 minutes after first formalin injection did not produce any significant changes in different phases, except for 1mg/ kg of naloxone, which produced a decrease in nociceptive response in phase2A (for phase 1: [F(2,17)=0.273; p=0.764], for interphase: [F(2,17)=1.266; p=0.307], for phase 2A: [F(2,17)=4.954; p=0.020], for phase 2B: [F(2, 17)=0.030; p=0.971]; Fig. 4). Naloxone (3mg/kg) administered 45 minutes after formalin injection produced a slight but not significant increase in nociceptive response in phase2A (for phase 1: [F(2,17)=0.196; p=0.824], for interphase: [F(2,17)=1.409; p=0.271], for phase 2A: [F(2,17)=0.344; p=0.714], for phase 2B: [F(2,17)=0.257; p=0.776]; Fig. 5).


Termination of Nociceptive Bahaviour at the End of Phase 2 of Formalin Test is Attributable to Endogenous Inhibitory Mechanisms, but not by Opioid Receptors Activation.

Azhdari-Zarmehri H, Mohammad-Zadeh M, Feridoni M, Nazeri M - Basic Clin Neurosci (2014)

Time scores of formalin induced nociceptive behaviours (mean ±S.E.M. of 7 or 8 rats per group) following naloxone injected minute 30 measured every 3 minutes for 90 minutes (A) and bar chart for them (B). The columns represent the mean of nociceptive score in each phase: phase 1 (1–7), interphase (8–14), phase 2A (15–60) and phase 2B (61–90), (B). Recording of the nociceptive behaviours began immediately after formalin injection (time 0) and was continued for the next 90 minutes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202598&req=5

Figure 0004: Time scores of formalin induced nociceptive behaviours (mean ±S.E.M. of 7 or 8 rats per group) following naloxone injected minute 30 measured every 3 minutes for 90 minutes (A) and bar chart for them (B). The columns represent the mean of nociceptive score in each phase: phase 1 (1–7), interphase (8–14), phase 2A (15–60) and phase 2B (61–90), (B). Recording of the nociceptive behaviours began immediately after formalin injection (time 0) and was continued for the next 90 minutes.
Mentions: Naloxone (1 and 3mg/kg) administered 30 minutes after first formalin injection did not produce any significant changes in different phases, except for 1mg/ kg of naloxone, which produced a decrease in nociceptive response in phase2A (for phase 1: [F(2,17)=0.273; p=0.764], for interphase: [F(2,17)=1.266; p=0.307], for phase 2A: [F(2,17)=4.954; p=0.020], for phase 2B: [F(2, 17)=0.030; p=0.971]; Fig. 4). Naloxone (3mg/kg) administered 45 minutes after formalin injection produced a slight but not significant increase in nociceptive response in phase2A (for phase 1: [F(2,17)=0.196; p=0.824], for interphase: [F(2,17)=1.409; p=0.271], for phase 2A: [F(2,17)=0.344; p=0.714], for phase 2B: [F(2,17)=0.257; p=0.776]; Fig. 5).

Bottom Line: While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet.While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection.While second injection of formalin, 5 minute after first injection, had no effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Sciences, Torbat heydariyeh University of Medical Sciences, Torbat heydariyeh, Iran.

ABSTRACT

Introduction: Formalin injection induces nociceptive bahaviour in phase I and II, with a quiescent phase between them. While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet. Phase II is a consequence of peripheral and central sensitization processes, which can lead to termination of the noxious stimuli responses; 45-60 minutes after formalin injection via possible recruitment of active inhibitory mechanisms which we have investigated in this study.

Methods: To test our hypothesis, in the first set of experiments, we evaluated nociceptive response after two consecutive injection of formalin (50µL, 2%), with intervals of 5 or 60 minutes. In the next set, formalin tests were carried out in companion with injection of Naloxone Hydrochloride, a non-selective antagonist of opioid receptors, pre-formalin injection and 30 and 45 minutes post formalin injection.

Results: While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection. While second injection of formalin, 5 minute after first injection, had no effect. Administration of naloxone (1mg/kg) decreased nociception in phase 2A; but had no effect on delayed termination of formalin test.

Discussion: The results of this study suggest the existence of an active inhibitory mechanism, other than the endogenous opioids, that is responsible for termination of nociceptive behaviour at the end of formalin test.

No MeSH data available.