Formalin Attenuates the Stress‐Induced Increase in Plasma Epinephrine Levels

Abstract

Subcutaneous (s.c.) injection of formalin into rats is frequently used as a painful stressor that produces a three-phase nociceptive response. We have shown previously that s.c. administered formalin (0.2 ml of 4% solution per 100 g body weight) unexpectedly attenuated the increase of plasma epinephrine levels in rats exposed to exteroceptive stressors (handling, immobilisation). To clarify the mechanism(s) responsible for this phenomenon, the effect of formalin applications on epinephrine plasma levels was investigated in various experimental conditions. Subcutaneous application of formalin combined with exposures of animals to an interoceptive stressor, insulin-induced hypoglycaemia, significantly attenuated the stress-induced increase in plasma epinephrine levels, whereas plasma norepinephrine levels remained highly elevated. Moreover, administration of formalin to unstressed animals also manifested signs of an attenuated epinephrine secretion. Interestingly, intraperitoneal administration of formalin did not reduce the elevated levels of plasma epinephrine. We suggest that formalin attenuates epinephrine secretion from the adrenal medulla most probably via irritation of s.c. somatosensory receptors. We hypothesise that the irritation of the primary sensory afferents fibres might reduce the activity of the sympathetic preganglionic neurones innervating adrenal medullary chromaffin cells. Further investigations are required to establish whether the observed reduction of epinephrine secretion from the adrenal medulla is controlled by either spinal or supraspinal neuronal circuits.

Prolactin Response to Formalin Is Related to the Acute Nociceptive Response and It Is Attenuated by Combined Application of Different Stressors

“…Immobilization also elicits an increase in plasma PRL levels with peak levels between 10 and 20 min [31, 32]. Previously, we have reported a sudden and strong reduction of plasma epinephrine levels in immobilized animal whether they were injected with formalin before or during immobilization [13, 14]. Our present results show that the administration of formalin cannot produce any further changes in hypothalamo-pituitary-adrenocortical (HPA) activity of immobilized rats (fig.…”

“…a significant increase in plasma norepinephrine (NE) levels, while change of plasma epinephrine (EPI) level is largely dependent on the concentration and the mode of application of the formalin solution [11, 12]. Our group has recently found that a single subcutaneous injection of formalin (0.2 ml of 4% solution/100 g BW) into the hind limb is able to attenuate the immobilization-induced increase of plasma catecholamines [13, 14]. …”

Effect of lesions of A5 or A7 noradrenergic cell group or surgical transection of brainstem catecholamine pathways on plasma catecholamine levels in rats injected subcutaneously by formalin

“…These observations are consistent with our previous reports showing that subcutaneous injection of 0.2 ml/100 g b.w. of 4% formalin attenuates stress-induced elevations of EPI in the plasma during first 15-30 minutes after application (Mravec et al 2004(Mravec et al , 2005. Formalin acts on EPI and NE levels in both sham-operated and transected rats.…”

“…Subcutaneous applications of formalin elicit pain behavioral responses (Abbott et al 1995), increase the blood pressure and heart rate (Culman et al 1997), and elevate the levels of NE, ACTH, corticosterone and prolactin in the plasma (Kant et al 1982;Pacak et al 1998;Vissers et al 2004). However, epinephrine secretion depends on the concentration and the volume of applied formalin solution (Culman et al 1997;Pacak et al 1998;Mravec et al 2004;Mravec et al 2005).…”

“…Moreover, administration of formalin evokes strong activity in the sympatho-neural system and hypothalamic-pituitary-adrenocortical axis. The activity of the adrenomedullary hormonal system depends on the concentration and volume of applied formalin solutions (Culman et al 1997;Pacak et al 1998;Mravec et al 2004Mravec et al , 2005.…”