Foot Hyperalgesia after Thoracic Burn Injury. Histochemical, Behavioral and Pharmacological Studies.

Abstract

Using behavioral, immunohistochemical and pharmacological studies, we report here that large thoracic burn injuries remotely induce hindpaw hyperalgesia during the healing stage. During 2-3 weeks after thoracic burn injury when the skin was regenerating from the wound, we observed by formalin test that the number of flinching behaviors significantly increased and simultaneously we observed by von Frey test that rats developed mechano-hyperalgesia in the foot. In the dorsal horn of the lumbar spinal cord in burn injured rats, c-Fos expression was significantly augmented after plantar formalin injection. The expression of m-opioid receptor in burn injured rats was significantly decreased compared with that in sham operated rats. The expression of substance P and CGRP in the lumbar dorsal horn was not different between burn and sham operated animals. We also observed that intrathecal administration of glutamate receptor antagonists (MK801 and CNQX) but not cyclooxigenase-2 antagonist (NS-398) reversed the threshold of von Frey test on the foot up to the control level at 2 weeks after injury. Collectively, we analyzed a new pain model showing foot hyperalgesia after thoracic burn injury and demonstrated that neurotransmission of glutamate was enhanced at the lumbar spinal cord level by immunocytochemistry and intrathecal administration of NMDA and non NMDA antagonists. Although the precise mechanism of how remote hyperalgesia at the healing stage developed in this model remains to be confirmed, substances such as trophic factors released from the regenerating skin may cause systemic hyperalgesia including in the foot.

Simultaneous Administration of Hyperbaric Oxygen Therapy and Antioxidant Supplementation with Filipendula ulmaria Extract in the Treatment of Thermal Skin Injuries Alters Nociceptive Signalling and Wound Healing

“…The opioid receptors in the dorsal horn response to nociceptive stimuli were significantly altered in the opioid receptors of knock-out animals [ 49 ]. The reason for the downregulation of MOR at the dorsal horn is unclear [ 50 , 51 ]. The increased plasma opioids reported during the acute period of burn injury may downregulate the receptor level.…”