Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain has not been examined. Previous studies in experimental animals suggest that the therapeutic effect of BV on arthritis is dependent on the site of administration. Because of this potential site specificity, the present study was designed to evaluate the anti-nociceptive effect of BV injections into a specific acupoint (Zusanli) compared to a non-acupoint in an animal model of chronic arthritis. Subcutaneous BV treatment (1 mg/kg per day) was found to dramatically inhibit paw edema caused by Freund's adjuvant injection. Furthermore, BV therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. the nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). These anti-nociceptive/anti-inflammatory effects of BV were observed from 12 days through 21 days post-BV treatment. In addition, BV treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. Finally, injection of BV into the Zusanli acupoint resulted in a significantly greater analgesic effect on arthritic pain as compared to BV injection in to a more distant non-acupoint. The present study demonstrates that BV injection into the Zusanli acupoint has both anti-inflammatory and anti-nociceptive effects on Freund's adjuvant-induced arthritis in rats. These findings raise the possibility that BV acupuncture may be a promising alternative medicine therapy for the long-term treatment of rheumatoid arthritis.

These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.

Rodent models of healing are considered limited because of the perception that rodent wounds heal by contraction while humans heal by re-epithelialization. The purpose of this report is to present evidence that simple murine excisional wounds provide a valid and reproducible wound model that heals by both contraction and re-epithelialization. Previous studies have shown that, although rodent wounds contract by up to 80%, much of this contraction occurs only after epithelial closure. To confirm these previous findings, we measured re-epithelialization and contraction in three separate mouse strains, (BALB/c, db/+ and db/db); re-epithelialization and contraction each accounted for ~40-60% of the initial closure of full thickness excisional wounds. After closure, the wound continues to contract and this provides the impression of dominant closure by contraction. In conclusion, the simple excisional rodent wound model produces a well-defined and readily identifiable wound bed over which the process of re-epithelialization is clearly measurable.

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Although previous reports have suggested that the sigma 1 (sigma(1)) receptor may be involved in pain sensation, its specific site of action has not been elucidated. The aim of present study was to determine the role of the spinal sigma(1) receptor in formalin-induced pain behavior, spinal cord Fos expression and phosphorylation of N-methyl-D-aspartate receptor subunit 1 (pNR1). Intrathecal (i.t.) pretreatment with the selective sigma(1) receptor antagonist, BD-1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide) (10-100 nmol) dose dependently reduced formalin-induced pain behaviors in second phase, but not first phase, of the formalin test. I.t. injection of BD-1047 also reduced formalin-evoked Fos expression and pNR1 at the protein kinase C-dependent site, serine-896 (Ser896) and the protein kinase A-dependent site, serine-897 (Ser897) in spinal dorsal horn.i.t. BMY-14802 ((alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol hydrochloride) (10-100 nmol, sigma(1) receptor antagonist and 5-HT(1A) receptor agonist) dose dependently reduced formalin-induced pain behaviors in both phases. However, the 5-HT(1A) receptor might not be involved in the antinociceptive effect of BMY-14802 on the second phase, since i.t. pretreatment with the 5-HT(1A) receptor antagonist propranolol ((S)-1-isopropylamino-3-(1-naphthyloxy)-2-propanol hydrochloride) (injected 10 min prior to i.t. BMY-14802) partially blocked the effect of BMY-14802 on the first phase of the formalin test but did not affect the inhibitory effect of BMY-14802 on the second phase. In addition, i.t. BMY-14802 significantly reduced formalin-evoked Fos expression and pNR1 (Ser896 and Ser897) expression in spinal dorsal horn. The results of this study suggest that selective blockage of spinal sigma(1) receptors can reduce pain behaviors, spinal cord Fos expression and pNR1 (Ser896 and Ser897) expression associated with the second phase of the formalin test.

Silk fibroin (SF) and alginate (AA) have been proved to be invaluable natural materials in the field of biomedical engineering. This study was designed to compare the wound healing effect of SF, AA and SF/AA-blended sponge (SF/AA) with clinically used Nu Gauze(TM) (CONT) in a rat full thickness wound model. Two circular skin wounds on the back of rat were covered with either of CONT, SF, AA or SF/AA. On the postoperative days of 3, 7, 10 and 14, residual wound area was calculated, and skin wound tissues were biopsied to measure the area of regenerated epithelium and collagen deposition as well as the number of proliferating cell nuclear antigen (PCNA)-immunoreactive cells. Half healing time (HT(50)) of SF/AA was dramatically reduced as compared with that of SF, AA or CONT. Furthermore, SF/AA significantly increased the size of re-epithelialization and the number of PCNA positive cells, whereas the effect of SF/AA on collagen deposition was not significantly different as compared with that of SF or AA. These results demonstrate that the wound healing effect of SF/AA is the best among other treatments including SF and AA, and this synergic effect is mediated by re-epithelialization via rapid proliferation of epithelial cell.

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ABSTRACT. In two previous reports, we have demonstrated that injection of bee venom (BV) into an acupoint produces a significant antinociceptive and anti-inflammatory effect in both a mouse model of visceral nociception and a rat model of chronic arthritis. Th e present study was designed to evaluate the potential antinociceptive effect of BV pretreatment on formalin-induced pain behavior and it associated spinal cord Fos expression in rats. Adult Sprague-Dawley rats were injected with BV directly into the Zusanli (ST36) acupoint or into an arbitrary non-acupoint located on the back. BV pretreatment into the Zusanli acupoint significantly decreased paw-licking time in the late phase of the formalin test. In contrast, BV injected into a non-acupoint in the back region did not suppress the paw-licking time. In addition, BV pretreatment into the Zusanli acupoint markedly inhibited spinal cord Fos expression induced by formalin injection. These findings indicate that BV pretreatment into the Zusanli acupoint has an antinociceptive effect on formalin-induced pain behavior. Bee venom (BV) from the honeybee consists of melittin, phospholipase A 2 , apamin, adolapin, mast cell degranulating peptide and several other bioactive substances [26]. Melittin and phospholipase A 2 , two major components of BV, are generally thought to play an important role in the induction of the irritation and allergic reaction associated with the bee stings. In this regard, intradermal injection of melittin produces a local hyperthermic effect in human [23]. Phospholipase A 2 is a membrane-associated phospholipid converting enzyme that is important in the production of arachidonic acid. Arachidonic acid is further metabolized by one of two enzyme pathways into various prostaglandins (by cyclooxygenase) or leukotrienes (by lipooxygenase). Subcutaneous BV injection into plantar surface of the rat paw produces characteristic pain behaviors including paw licking and flinching [26] while BV administration in cats has been shown to produce prolonged and tonic nociceptive responses associated with changes in the firing of spinal cord neurons [7]. Chen and his colleagues have since published several reports that have elucidated some of the mechanisms underlying BV-induced nociception in rats and cats [7-13, 27, 28, 34, 35].In contrast to this recent focus on BV's nociceptive effects, Kwon and his co-workers have reported that longterm treatment with BV at a dose of 1 mg/kg/day produces a significant antinociceptive and anti-inflammatory effect on the Freund's complete adjuvant-induced arthritis in rats [24]. Although natural BV produces irritation when injected subcutaneously, injection of diluted BV, particularly into an acupoint, can reduce chronic nociception and inflammation. Thus Kwon et al. have shown that BV treatment into an acupoint can significantly reduce arthritisassociated edema and nociceptive responses [24]. In addition, BV injection into the Zhongwan acupoint significantly reduces the number of abdominal stretches induced by intraper...