mdl-100907 and Burns

Major thermal injuries lead to a systemic inflammatory response with systemic capillary leakage and multiple organ dysfunction. This systemic inflammatory response is induced by a variety of immunmodulative molecules including TNFα and serotonin. Unspecific serotonin antagonism leads to reduced macromolecular efflux in rat mesenteries after burn plasma transfer. The aim of the present study was to evaluate the effect of specific 5-HT2a antagonism on early burn edema.. Donor rats (DR) underwent thermal injury (100 °C water, 30% BSA, 12 s) for positive controls. For negative controls, DR underwent sham burn (37 °C water, 30% BSA, 12 s). DR plasma (harvested 4 h post-trauma) was transferred to healthy individuals for positive controls. Study rats received burn plasma (BP) and a Bolus injection of Ketanserin (Ket) (1 mg kg(-1) body weight). Negative controls underwent sham burn plasma infusion. Intravital microscopy was performed in mesenteric venules (0/60/120 min). Edema was assessed by FITC-albumin extravasation. Additionally, leukocyte rolling and sticking (cells mm(-2)) as well as microhemodynamic parameters were assessed.. Significant systemic capillary leakage was observed after BP transfer at 120 min and additional administration of Ket attenuated the postburn edema to sham burn levels. Ket also leads to significantly decreased leukocyte-endothelial interactions when compared to positive controls.. 5-HT2a antagonism reduces plasma extravasation after burn plasma transfer in healthy individuals. The influence of leukocyte-endothelial interactions on postburn edema remains unclear.

Topics: Animals; Burns; Edema; Endothelium, Vascular; Hemodynamics; Ketanserin; Leukocytes; Mesentery; Rats, Wistar; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Antagonists; Serum Albumin

Inflammation or injury of peripheral tissue causes release of chemical mediators, including 5-hydroxytryptamine (5-HT), which is involved in the facilitation of nociceptive transmission and the induction of hyperalgesia. The present study examined the effect of a selective 5-HT2A receptor antagonist, sarpogrelate, on hyperalgesia and allodynia induced by thermal injury in rats. Mild thermal injury to the hindpaw produces thermal hyperalgesia in the injured area (primary thermal hyperalgesia) and mechanical allodynia in sites adjacent to the primary area (secondary mechanical allodynia). Mechanical allodynia was assessed by paw withdrawal thresholds using von Frey filaments, and thermal hyperalgesia was assessed by paw withdrawal latencies upon exposure to a radiant heat source. Intraperitoneal administration (30-100 mg/kg) or local injection (30-300 microg) of sarpogrelate 10 min prior to thermal injury attenuated secondary mechanical allodynia in a dose-dependent manner. Intraperitoneal administration (3-100 mg/kg) or local injection (30-300 microg) of sarpogrelate 10 min prior to thermal injury attenuated primary thermal hyperalgesia in a dose-dependent manner. Intraplantar injection of sarpogrelate (300 microg) to the contralateral hindpaw had no effect on primary thermal hyperalgesia or secondary mechanical allodynia in the ipsilateral paw. The tissue concentration of 5-HT was measured using microdialysis. Concentrations of 5-HT increased after thermal injury in both primary and secondary areas, and the increase was not attenuated by pretreatment with sarpogrelate (100 mg/kg, i.p.). These data suggest that 5-HT released in peripheral tissues after thermal injury sensitizes primary afferent neurons and produces mechanical allodynia and thermal hyperalgesia via peripheral 5-HT2A receptors.

Topics: Animals; Burns; Dose-Response Relationship, Drug; Hot Temperature; Hyperalgesia; Male; Pain Threshold; Physical Stimulation; Rats; Rats, Wistar; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Succinates; Touch; Treatment Outcome