The Effect of Simultaneous Steroid and Verapamil Injection on Scar Formation in the Incisional Wound of Rat

The wound healing in adult mammals is a complex process that inevitably leaves scar. Various treatment modalities have been investigated to minimize the scar formation, and a few of them succeeded. Intra-lesional injection of steroids is one of the methods that have been widely accepted for the treatment of specific scars such as keloids or hypertrophic scars. On the other hand, there have been some attempts made to reduce the scar by enhancing the expression of matrix metalloproteinase(MMPs) because it results in degradation of collagens in scar tissues. Verapamil, a calcium channel blocker, was one of the few factors promoting the expression of MMPs such as collagenases by altering the shape of fibroblasts from a bipolar spindle type to a round one. No investigation, however, has been done to elucidate the effect of simultaneous intra- lesional injection of steroid and verapamil to wounds on early scar formation. To investigate the effect of scar reduction by injecting steroid and verapamil simultaneously, we examined morphologic finding of tissue and we measured width of scar followed by incision wounds treated with normal saline(Control group), steroid(Group A), verapamil(Group B) and both steroid and verapamil (Group C), respectively. The scar width significantly reduced in Group B and Group C 2 and 4 weeks after the incision and in Group A 8 weeks after incision, in comparison with control group. At that time the scar width in Group C significant reduced compared to those of other groups. Furthermore the collagen fibers were less, thicker and more regularly arranged in the scar tissue in group C 8 weeks after incision than those in the other groups and their structure was most close to the normal one of the dermis. The contour of fibroblasts in Group B and Group C looked rounder than that in Group A and control group. In conclusion, simultaneous intra-lesional injection of steroid and verapamil decreases collagen deposition into the wound and subsequently minimize scar width.

Effects of electrical stimulation of brainstem nuclei on dorsal horn neuron responses to mechanical stimuli in a rat model of neuropathic pain

The aim of the present study is to examine the brainstem sites where the electrical stimulation produces a suppression of dorsal horn neuron responses of neuropathic rats. An experimental neuropathy was induced by a unilateral ligation of L5-L6 spinal nerves of rats. Ten to 15 days after surgery, the spinal cord was exposed and single-unit recording was made on wide dynamic range (WDR) neurons in the dorsal horn. Neuronal responses to mechanical stimuli applied to somatic receptive fields were examined to see if they were modulated by electrical stimulation of various brainstem sites. Electrical stimulation of periaqueductal gray (PAG), n. raphe magnus (RMg) or n. reticularis gigantocellularis (Gi) significantly suppressed responses of WDR neurons to both noxious and non-noxious stimuli. Electrical stimulation of other brainstem areas, such as locus coeruleus. (LC) and n. reticularis paragigantocellularis lateralis (LPGi), produced little or no suppression. Microinjection of morphine into PAG, RMg, or Gi also produced a suppression as similar pattern to the case of electrical stimulation, whereas morphine injection into LC or LPGi exerted no effects. The results suggest that PAG, NRM and Gi are the principle brainstem nuclei involved in the descending inhibitory systems responsible for the control of neuropathic pain. These systems are likely activated by endogenous opioids and exert their inhibitory effect by acting on WDR neurons in the spinal cord.