• The Korean Journal of Pain
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• v.14 no.2
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• pp.142-149
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• 2001

Background: The expression of the proto-oncogene c-fos in spinal cord neurons following various noxious stimuli has been demonstrated in numerous studies. However, the pattern of expression of c-fos after incisional stimulus has not been evaluated. This study was designed to examine c-fos expression in an incisional pain model of rats. Methods: A 1 cm longitudinal incision was made through the skin, fascia and muscle of the plantar aspect of the hindpaw in enflurane-anesthetized rats. Withdrawal responses were measured using von Frey filaments at areas around the wound before surgery and for the next 48 hours. The expression of c-fos protein in the lumbar spinal cord was examined by immunohistochemistry. Results: After incision, c-fos was strongly expressed within laminae I, II, III, IV, V and VI ipsilateral to the incision. C-fos positive neurons were detected in the controlateral site, as well. Conclusions: These studies suggest that spinal c-fos protein may not be used as a specific marker for spinal nociceptive processing in an incisional pain model.

• The Korean Journal of Pain
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• v.37 no.4
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• pp.310-319
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• 2024

Background: This study aimed to investigate the analgesic and preventive effect of low-level laser therapy (LLLT) on the incisional pain model and spinal nerve ligation (SNL) model in rats and identify the possible mechanisms of action. Methods: Male Sprague-Dawley rats were used, divided into different treatment groups. The single application group received LLLT before or after skin incision or SNL. The consecutive application group received LLLT for six consecutive days post-incision, three days pre-incision, or three consecutive days pre-SNL. The control group underwent skin incision or SNL without LLLT. The von Frey test was used to quantify the pain associated with mechanical allodynia. Pro-inflammatory cytokine level and alterations in nerve growth factor (NGF) expression were measured by using ELISA and immunohistochemistry, respectively in the skin, muscle of the paw, and spinal cord dorsal horn (SCDH). Results: In the incisional pain model, LLLT showed significant analgesic and preventive effect. LLLT ameliorated SNL-induced mechanical allodynia but LLLT had no preventive effect. LLLT decreased interleukin-1β (IL-1β) expression levels in the skin, muscle, and SCDH and reduced the optical density of skin and spinal cord NGF in the incisional pain model. Conclusions: LLLT alleviated incisional pain and neuropathic pain caused by SNL in rats, and reduced the levels of IL-1β and NGF in the peripheral tissue and SCDH in the incisional pain model. LLLT might be effective in patients with post-operative pain and peripheral neuropathic pain.

• The Korean Journal of Pain
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• v.34 no.2
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• pp.185-192
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• 2021

Background: It is known that some analgesics as well as pain can affect the immune system. The aim of this study was to investigate the analgesic effect and immunomodulation of pregabalin (PGB) in a mouse incisional pain model. Methods: A postoperative pain model was induced by hind paw plantar incision in male BALB/c mice. Mice were randomly divided into four groups (n = 8): a saline-treated incision (incision), PGB-treated incision (PGB-incision), sham controls without incision or drug treatment (control), and a PGB-treated control (PGB-control). In the PGB treated groups, PGB was administered intraperitoneally (IP) 30 minutes before and 1 hour after the plantar incision. Changes of the mechanical nociceptive thresholds following incision were investigated. Mice were euthanized for spleen harvesting 12 hours after the plantar incision, and natural killer (NK) cytotoxicity to YAC 1 cells and lymphocyte proliferation responses to phytohemagglutinin were compared among these four groups. Results: Mechanical nociceptive thresholds were decreased after plantar incision and IP PGB administration recovered these decreased mechanical nociceptive thresholds (P < 0.001). NK activity was increased by foot incision, but NK activity in the PGB-incision group was significantly lower than that in the Incision group (P < 0.001). Incisional pain increased splenic lymphocyte proliferation, but PGB did not alter this response. Conclusions: Incisional pain alters cell immunity of the spleen in BALB/c mice. PGB showed antinocieptive effect on mouse incisional pain and attenuates the activation of NK cells in this painful condition. These results suggest that PGB treatment prevents increases in pain induced NK cell activity.

• The Korean Journal of Pain
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• v.26 no.2
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• pp.125-129
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• 2013

Background: 5-hydroxytryptamine 3 (5-HT3) receptors have been known to be associated with the modulation of nociceptive transmission. However, it is uncertain whether 5-HT3 plays a role in the antinociceptive or pronociceptive pathway for incisional pain. In this study, we evaluated the effects of palonosetron, a 5-HT3 receptor antagonist, on incisional pain in rats when administered intrathecally or intraplantarly. Methods: An intrathecal catheter was implanted through the cisterna magna and placed in the intrathecal space of rats. An incision in the plantaris muscle of the right hind paw was done under anesthesia with sevoflurane. Withdrawal thresholds were evaluated with the von Frey filament after 2 hours. Palonosetron (0.5 and 0.1 ${\mu}g$ intrathecally; 0.5 ${\mu}g$ intraplantarly) was administered and the thresholds were observed for 4 hours. Results: Mechanical hypersensitivity developed after the incision. Intrathecal palonosetron (0.5 ${\mu}g$ and 0.1 ${\mu}g$) did not alter the paw withdrawal threshold. Intraplantar palonosetron (0.5 ${\mu}g$) also did not change the paw withdrawal threshold. Conclusions: Intrathecal and intraplantar palonosetron (0.5 ${\mu}g$) had no effect on modulating the mechanical hypersensitivity in the incisional pain model of rats.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.92-99
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• 2007

Background: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. Methods: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. Results: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. Conclusions: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.2
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• pp.97-105
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• 2022

Background: The pentadecapeptide BPC-157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. Peptides have potent anti-inflammatory effects on periodontal tissues in rats with periodontitis. Few studies have investigated the effect of BPC-157 on pain after dental procedures or oral surgeries. The purpose of the present study was to investigate the antinociceptive effects of BPC-157 on postoperative incisional pain in rats. Methods: Sprague-Dawley rats were randomly divided into five groups: control (saline with the same volume), BPC10 (10 ㎍/kg of BPC-157), BPC20 (20 ㎍/kg of BPC-157), BPC40 (40 ㎍/kg of BPC-157), and morphine (5 mg/kg of morphine). A 1-cm longitudinal incision was made through the skin, fascia, and muscle of the plantar aspect of the hind paw in isoflurane-anesthetised rats. Withdrawal responses were measured using von Frey filaments at 0, 2, 6 h and 4, 7 d after incision. The formalin test was also performed to differentiate its anti-nociceptive effect from an inflammatory reaction or central sensitization. Pain behavior was quantified periodically in phases 1 and 2 by counting the number of flinches in the ipsilateral paw after injection with 30 µL of 5% formalin. Results: The threshold of mechanical allodynia was significantly increased in the BPC10, BPC20, BPC40 and morphine groups compared with that in the control group at 2 h. These increasing thresholds then returned to the levels of the control group. The BPC-157 group showed a much higher threshold at 4 days after incision than the control group. The thresholds of the BPC groups, except the morphine group, were normalized 7 days after incision. The flinching numbers of the BPC10, BPC20, BPC40 and morphine groups were significantly decreased in phase 1, but there was no decrease in the BPC-157 groups except the morphine group in phase 2. Conclusions: BPC-157 was effective only for a short period after incision. It was also effective during phase 1 but not during phase 2, as determined by the formalin test. BPC-157 might have a short antinociceptive effect, even though it has anti-inflammatory and wound healing effects.

• The Korean Journal of Pain
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• v.34 no.2
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• pp.165-175
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• 2021

Background: Management of pain from open wounds is a growing unmet healthcare need. However, the models available to study pain from wounds or to develop analgesics for the patients suffering from them have primarily relied on incisional models. Here, we present the first characterized and validated model of open wound pain. Methods: Unilateral full-skin excisional punch biopsy wounds on rat hind paws were evaluated for evoked pain using withdrawal responses to mechanical and thermal stimulation, and spontaneous pain was measured using hind paw weight distribution and guarding behavior. Evaluations were done before wounding (baseline) and 2-96 hours post-wounding. The model was validated by testing the effects of buprenorphine and carprofen. Results: Pain responses to all tests increased within 2 hours post-wounding and were sustained for at least 4 days. Buprenorphine caused a reversal of all four pain responses at 1 and 4 hours post-treatment compared to 0.9% saline (P < 0.001). Carprofen decreased the pain response to thermal stimulation at 1 (P ≤ 0.049) and 4 hours (P < 0.011) post-treatment compared to 0.9% saline, but not to mechanical stimulation. Conclusions: This is the first well-characterized and validated model of pain from open wounds and will allow study of the pathophysiology of pain in open wounds and the development of wound-specific analgesics.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.183-191
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• 2018

Background: Ginseng saponin has long been used as a traditional Asian medicine and is known to be effective in treating various kinds of pain. Ginsenoside Rf is one of the biologically active saponins found in ginseng. We evaluated ginsenoside Rf's antinociceptive and anti-inflammatory effects, and its mechanism of action on adrenergic and serotonergic receptors, in an incisional pain model. Methods: Mechanical hyperalgesia was induced via plantar incision in rats followed by intraperitoneal administration of increasing doses of ginsenoside Rf (vehicle, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, and 2 mg/kg). The antinociceptive effect was also compared in a Positive Control Group that received a ketorolac (30 mg/kg) injection, and the $Na{\ddot{i}}ve$ Group, which did not undergo incision. To evaluate the mechanism of action, rats were treated with prazosin (1 mg/kg), yohimbine (2 mg/kg), or ketanserin (1 mg/kg) prior to receiving ginsenoside Rf (1.5 mg/kg). The mechanical withdrawal threshold was measured using von Frey filaments at various time points before and after ginsenoside Rf administration. To evaluate the anti-inflammatory effect, serum interleukin $(IL)-1{\beta}$, IL-6, and tumor necrotizing $factor-{\alpha}$ levels were measured. Results: Ginsenoside Rf increased the mechanical withdrawal threshold significantly, with a curvilinear dose-response curve peaking at 1.5 mg/kg. $IL-1{\beta}$, IL-6, and tumor necrotizing $factor-{\alpha}$ levels significantly decreased after ginsenoside Rf treatment. Ginsenoside Rf's antinociceptive effect was reduced by yohimbine, but potentiated by prazosin and ketanserin. Conclusion: Intraperitoneal ginsenoside Rf has an antinociceptive effect peaking at a dose of 1.5 mg/kg. Anti-inflammatory effects were also detected.

• The Korean Journal of Pain
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• v.32 no.2
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• pp.87-96
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• 2019

Background: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. Methods: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG ($10{\mu}g$, $30{\mu}g$, $100{\mu}g$, and $300{\mu}g$) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG $300{\mu}g$ in order to assess the involvement of SOG with an opioid receptor. The protein levels of the ${\delta}$-opioid receptor, ${\kappa}$-opioid receptor, and ${\mu}$-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. Results: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of $300{\mu}g$ at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was $191.3{\mu}g$ (95% confidence interval, 102.3-357.8). The antinociceptive effects of SOG ($300{\mu}g$) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. Conclusions: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.

• The Korean Journal of Pain
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• v.33 no.4
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• pp.326-334
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• 2020

Background: In this study, we sought to evaluate whether systemic propentofylline (PPF) has antiallodynic effects in a rat model of postoperative pain, and to assess the mechanism involved. Methods: After plantar incision, rats were intraperitoneally injected with various doses of PPF to evaluate its antiallodynic effect. To investigate the involved mechanism, rats were intraperitoneally injected with yohimbine, dexmedetomidine, prazosin, naloxone, atropine or mecamylamine, following the incision of the rat hind paws, and then PPF was administered intraperitoneally. The mechanical withdrawal threshold (MWT) was evaluated using von Frey filaments at various time points and serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured to determine the inflammatory response level. Results: MWT was significantly increased after intraperitoneal injection of 30 mg/kg of PPF when compared with the control group. Injection of PPF and yohimbine, atropine or mecamylamine showed significant decreases in the MWT, while injection of PPF and dexmedetomidine showed a significant increase. Systemic administration of PPF inhibited the post-incisional increase in serum level of TNF-α and IL-1β. Conclusions: Systemic administration of PPF following surgery presented antiallodynic effects in a rat model of postoperative pain. The antiallodynic effects against mechanical allodynia could be mediated by α-adrenergic and cholinergic receptors.