Elsevier

Life Sciences

Volume 74, Issue 16, 5 March 2004, Pages 1973-1979
Life Sciences

Influence of surgical pain stress on the blood-brain barrier permeability in rats

https://doi.org/10.1016/j.lfs.2003.07.054Get rights and content

Abstract

Effect of surgical pain stress on the blood-brain barrier permeability was investigated in rats. The animals were divided into four groups: Group 1: control, Group 2: immobilization stress, Group 3: acute hypertension, Group 4: immobilization stress + surgical pain stress.Bilateral hid paw surgical wounds for cannulations were applied in animals' inguinal regions under diethyl-ether anesthesia, then the animals were awaken from anesthesia to produce surgical pain stress. Evans-blue was used as a blood-brain barrier tracer. There is no significantly blood-brain barrier breakdown after short-time immobilization stress, but after adrenalin hypertension blood-brain barrier permeability was increased especially on frontal and occipital cortices in 50% of the animals. Surgical pain stress increased blood-brain barrier permeabiliy in comparison to acute adrenalin-induced hypertension (p < 0.01). In surgical pain stress-induced animals distinct Evans-blue leakage was observed in the occipital, frontal and parieto-temporal cortices.

Introduction

The microvasculature of central nervous system is characterized by tight-junctions between endothelial cells (Huber et al., 2001a). Fenestration between the vascular endothelial cells of most organs are not found within the mammalian central nervous system. In addition they express a very low rate of pinocytotic activity. These structure and function of cerebral endothelial cells are called blood-brain barrier.

The blood-brain barrier restricts movement of water-soluble substances, neurotransmitters, lipid insoluble substances such as peptides, hormones, toxins between blood and central nervous system.

Breakdown of the blood-brain barrier in humans and experimental animals in various pathological conditions, including hypertension, convulsions, ischemia, hypoglycemia, inflammation and central nervous system neoplasm has been well demonstrated using tracers, such as horseradish peroxidase, Evans-blue, 14C-inulin and 131I-albumin Abbott, 2002, Greenwood, 1991, Öztaş, 1998, Öztaş and Türkel, 2001.

Several investigations have indicated that the application of stress influences blood-brain barrier permeability in both human beings (Hanin, 1996) and experimental animals Esposito et al., 2001, Madrigal et al., 2002, Sharma et al., 1994, Sinton et al., 2000. Sharma and Dey have shown that eight hours immobilization stress in young rats has increased blood-brain barrier permeability (Sharma and Dey, 1986). More recently Skultetyovă et al have also reported that in rats exposed to a short lasting immobilization stress, tissue albumin concentration were elevated in the hippocampus, cerebellum, brainstem and hypothalamus (Skultetyovă et al., 1998).

The exposure of animals to long lasting or short lasting stress conditions, Sharma et al., 1992, Skultetyovă et al., 1998 such as immobilization for 30 min or 4–8 h; heat stress for 4 h or starvation (Angel, 1969), was shown to result in breakdown of the blood-brain barrier.

On the other hand, pain is a very important stress in the human life. Huber et al have examined three different inflammatory pain models (acute, short term and long term) (Huber et al., 2001b). They have investigated blood-brain barrier permeability in vivo after peripheral inflammation stimuli. Each of the three inflammatory pain models, produced significant increases in blood-brain barrier permeability. They have shown that inflammation- mediated pain states alter both the functional and molecular properties of the blood-brain barrier (Huber et al., 2001b). With the use of this approach, we compared surgical pain model to determine blood-brain barrier permeability in the rats. No studies have directly examined the effects of surgical pain on the blood-brain barrier permeability in vivo. Thus, the goal of this study was to examine the direct effect of surgical acute pain on the permeability of the blood-brain barrier in rats. A brief account of the results have appeared in abstract form (Arslan et al., 2003).

Section snippets

Material and methods

The experiments were performed on Wistar albino rats weighing between 280–310 g. The rats were divided into four groups: Group 1: control rats (n = 10), Group 2: immobilization stress (n = 10), Group 3: acute hypertension (n = 10), Group 4: immobilization stress + surgical pain stress (n = 10).

All animals were immobilized under diethyl-ether anesthesia. In group 1,3,4 femoral artery was cannulated for recording mean arterial blood pressure. Mean arterial blood pressure was recorded by

Results

The degree of blood-brain barrier breakdown and mean arterial blood pressure before and after drug administration are presented in Table 1. In all rats a single rapid intravenous administration of adrenalin resulted in an immediate increase in mean arterial blood pressure. The initial mean arterial blood pressure was 110 ± 14 mmHg in a acute hypertensive animals (group 3) and 104 ± 9 mmHg in pain group animals. This pressure rapidly increased to 176 ± 12 mmHg in adrenalin group, after adrenalin

Discussion

This is the first study that examines the effects of wound pain-induced stress on the blood-brain barrier permeability in rats. In this study, group 1 (the control group) and group 3 (acute hypertension group) were under non-pain stress conditions, because these animals were under the diethyl-ether anesthesia during the whole experiments. But group 2 (immobilization stress) and group 4 (immobilization stress+surgical pain stress) were awakened from anesthesia to aware of their stresses during

Conclusion

Surgical pain stress breakdowns blood-brain barrier permeability. Pain is a very important condition both physiologically and pathologically in human life.

Labour pain, dental pain and surgical pain are well known circumtances. This must be considered in clinics in intense pain conditions.

References (27)

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