The aim of the present study was to develop an animal model for evaluation of temporomandibular (TMJ) nociception under TMJ inflammation. We also investigated the participation of IL-1β in inflammation-induced TMJ nociception. Experiments were carried out using male Sprague-Dawley rats. Intra-articular injection of 3% formalin was administered to evaluate hyperalgesia 3 days after CFA injection. Intra-articular injection of 3% formalin did not produce nociceptive behavior in normal rats. Although intra-articular injection of 3 doses of CFA produced TMJ inflammation, only 1:3 diluted CFA produced hyperalgesia when formalin was injected intra-articularly 3 days after CFA injection. Co-administration of IL-1 receptor inhibitor with formalin into the TMJ cavity 3 days after CFA injection was performed. Co-administration of IL-1 receptor inhibitor significantly inhibited formalin-induced hyperalgesia in rats with CFA-induced TMJ inflammation. These results suggested that intra-articular injection of formalin produced hyperalgesia under chronic TMJ inflammation. Moreover, IL-1β plays an important role in TMJ hyperalgesia under chronic inflammation and blockade of IL-1β is a potential therapeutic target for inflammatory TMJ pain.
Animals ; Formaldehyde ; Humans ; Hyperalgesia ; Inflammation* ; Injections, Intra-Articular ; Interleukin-1 ; Male ; Models, Animal ; Nociception* ; Rats* ; Rats, Sprague-Dawley ; Temporomandibular Joint

No abstract available.
Kidney* ; Transplants* ; Tuberculosis*

The present study was performed to investigate the effects of intra-articular injection of interleukin-1beta (IL-1beta) on the formalin-induced temporomandibular joint (TMJ) pain. Under anesthesia, a 30-gauge needle was introduced into the right TMJ region for injection of formalin. Microinjection of 50 microliter of 5% formalin significantly produced noxious scratching behavioral response, and the scratching behavior lasted for 40 min. Although the responses produced by formalin injection were divided into two phases, the response of 1st phase did not significantly differ from the scratching behavior response in the saline-treated group. We examined the effects of intra-articular injection of IL-1beta on the number of noxious behavioral responses produced by 50microliter of 5% formalin injection. Intra-articular injection of 100 pg and 1 ng of IL-1beta significantly increased the number of behavioral responses of the 2nd phase, while 10 pg of IL-1beta did not change the formalin-induced behavioral responses. To investigate whether IL-1 receptor was involved in the intra-articular administration of IL-1beta-induced hyperalgesic response, IL-1 receptor antagonist (IL- ra, 50 ng) was administrated together with IL-1beta injection. IL-1beta receptor antagonist blocked IL-1beta- induced hyperalgesic response in the TMJ formalin test. These results suggest that intra-articular injection of IL-1beta facilitated the transmission of nociceptive information in the TMJ area.
Anesthesia ; Animals ; Cytokines ; Formaldehyde ; Hyperalgesia ; Injections, Intra-Articular* ; Interleukin-1 ; Interleukin-1beta ; Microinjections ; Needles ; Pain Measurement ; Rats* ; Temporomandibular Joint*

The study aimed to investigate the role of peripheral NLR family pyrin domain-containing 3 protein (NLRP3) in inflammatory pain development in the orofacial area. Male Sprague–Dawley rats were used in experiments, with orofacial formalin-induced pain behavior and complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia as chronic inflammatory pain models. Administration of 5% formalin produced biphasic nociceptive behavior, and subcutaneous pretreatment with MCC950 (50 and 100 μg/50 μL), an NLRP3 inhibitor, remarkably attenuated nociceptive behavior during the second phase. Subcutaneous CFA injection induced thermal hyperalgesia 1 day after injection, which persisted for 7 days. Five days after CFA injection, subcutaneous treatment with MCC950 (50 and 100 μg/50 μL) significantly attenuated thermal hyperalgesia. Additionally, subcutaneous injection of BMS-986299 (50 and 100 μg/50 μL), an NLRP3 agonist, induced significant nociceptive behavior for 1 hour in naïve rats. Pretreatment with an interleukin-1β (IL-1β) receptor antagonist blocked the nociceptive behavior produced by subcutaneous injection of BMS-986299 (100 μg/50 μL);however, treatment with a hypoxia-inducible factor 1α inhibitor did not. These findings suggest the involvement of the peripheral NLRP3 and IL-1β pathway in chronic inflammatory pain development in the orofacial area, highlighting the potential of blocking this pathway as a strategy for developing future inflammatory pain treatment drugs.

The study aimed to investigate the role of peripheral NLR family pyrin domain-containing 3 protein (NLRP3) in inflammatory pain development in the orofacial area. Male Sprague–Dawley rats were used in experiments, with orofacial formalin-induced pain behavior and complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia as chronic inflammatory pain models. Administration of 5% formalin produced biphasic nociceptive behavior, and subcutaneous pretreatment with MCC950 (50 and 100 μg/50 μL), an NLRP3 inhibitor, remarkably attenuated nociceptive behavior during the second phase. Subcutaneous CFA injection induced thermal hyperalgesia 1 day after injection, which persisted for 7 days. Five days after CFA injection, subcutaneous treatment with MCC950 (50 and 100 μg/50 μL) significantly attenuated thermal hyperalgesia. Additionally, subcutaneous injection of BMS-986299 (50 and 100 μg/50 μL), an NLRP3 agonist, induced significant nociceptive behavior for 1 hour in naïve rats. Pretreatment with an interleukin-1β (IL-1β) receptor antagonist blocked the nociceptive behavior produced by subcutaneous injection of BMS-986299 (100 μg/50 μL);however, treatment with a hypoxia-inducible factor 1α inhibitor did not. These findings suggest the involvement of the peripheral NLRP3 and IL-1β pathway in chronic inflammatory pain development in the orofacial area, highlighting the potential of blocking this pathway as a strategy for developing future inflammatory pain treatment drugs.

The study aimed to investigate the role of peripheral NLR family pyrin domain-containing 3 protein (NLRP3) in inflammatory pain development in the orofacial area. Male Sprague–Dawley rats were used in experiments, with orofacial formalin-induced pain behavior and complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia as chronic inflammatory pain models. Administration of 5% formalin produced biphasic nociceptive behavior, and subcutaneous pretreatment with MCC950 (50 and 100 μg/50 μL), an NLRP3 inhibitor, remarkably attenuated nociceptive behavior during the second phase. Subcutaneous CFA injection induced thermal hyperalgesia 1 day after injection, which persisted for 7 days. Five days after CFA injection, subcutaneous treatment with MCC950 (50 and 100 μg/50 μL) significantly attenuated thermal hyperalgesia. Additionally, subcutaneous injection of BMS-986299 (50 and 100 μg/50 μL), an NLRP3 agonist, induced significant nociceptive behavior for 1 hour in naïve rats. Pretreatment with an interleukin-1β (IL-1β) receptor antagonist blocked the nociceptive behavior produced by subcutaneous injection of BMS-986299 (100 μg/50 μL);however, treatment with a hypoxia-inducible factor 1α inhibitor did not. These findings suggest the involvement of the peripheral NLRP3 and IL-1β pathway in chronic inflammatory pain development in the orofacial area, highlighting the potential of blocking this pathway as a strategy for developing future inflammatory pain treatment drugs.

The study aimed to investigate the role of peripheral NLR family pyrin domain-containing 3 protein (NLRP3) in inflammatory pain development in the orofacial area. Male Sprague–Dawley rats were used in experiments, with orofacial formalin-induced pain behavior and complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia as chronic inflammatory pain models. Administration of 5% formalin produced biphasic nociceptive behavior, and subcutaneous pretreatment with MCC950 (50 and 100 μg/50 μL), an NLRP3 inhibitor, remarkably attenuated nociceptive behavior during the second phase. Subcutaneous CFA injection induced thermal hyperalgesia 1 day after injection, which persisted for 7 days. Five days after CFA injection, subcutaneous treatment with MCC950 (50 and 100 μg/50 μL) significantly attenuated thermal hyperalgesia. Additionally, subcutaneous injection of BMS-986299 (50 and 100 μg/50 μL), an NLRP3 agonist, induced significant nociceptive behavior for 1 hour in naïve rats. Pretreatment with an interleukin-1β (IL-1β) receptor antagonist blocked the nociceptive behavior produced by subcutaneous injection of BMS-986299 (100 μg/50 μL);however, treatment with a hypoxia-inducible factor 1α inhibitor did not. These findings suggest the involvement of the peripheral NLRP3 and IL-1β pathway in chronic inflammatory pain development in the orofacial area, highlighting the potential of blocking this pathway as a strategy for developing future inflammatory pain treatment drugs.

The present study investigated the effects of QX-314 on inflammatory pain of the temporomandibular joint (TMJ). Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Under anesthesia, the TMJ of each animal was injected with 50 microL of formalin (5%). The number of noxious behavioral responses, including rubbing or scratching of the facial region including the TMJ area, was recorded over 9 sequential 5 min intervals for each animal. Although 2.5% QX-314 did not affect formalin-induced nociceptive behavior, administration of 5% QX-314 with formalin significantly decreased the number of scratches produced by the formalin injection. Co-administration of capsaicin, a TRPV1 agonist, with 2.5% QX-314 produced significant anti-nociceptive effects whereas 2.5% QX-314 alone did not. However, the co-administration of capsaicin did not enhance the anti-nociceptive effects in the 5% QX-314-treated rats. Moreover, the co-administration of capsazepine, a TRPV1 antagonist, did not attenuate anti-nociceptive effects in the 5% QX-314-treated rats. These findings suggest that TRPV1 is effective in the transport of low but not high doses of QX-314. Moreover, a high dose of QX-314, which is not mediated by peripheral TRPV1 activity, may be viable therapeutic strategy for inflammatory pain in the TMJ.
Anesthesia ; Animals ; Capsaicin* ; Formaldehyde ; Humans ; Male ; Pain Measurement ; Rats* ; Rats, Sprague-Dawley ; Temporomandibular Joint*

The present study was to evaluate effects of vitamin E on intravenous administration of lidocaine-induced antinociception. Experiments were carried out using male Sprague-Dawley rats. Orofacial formalin-induced nociceptive behavioral responses were used as the orofacial animal pain model. Subcutaneous injection of formalin produced significant nociceptive scratching behavior. Intraperitoneal injection of 5 and 10 mg/kg of lidocaine attenuated formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. Intraperitoneal injection of 1 g/kg of vitamin E also attenuated the formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. However, low dose of vitamin E (0.5 g/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. The present study also investigated effects of intraperitoneal injection of both vitamin E and lidocaine on orofacial formalin-induced behavioral responses. Vehicle treatment affected neither formalin-induced behavioral responses nor lidocaine-induced antinociceptive effects. However, intraperitoneal injection of 0.5 g/kg of vitamin E enhanced the lidocaine-induced antinociceptive effects in the 2nd phase compared to the vehicle-treated group. Intraperitoneal injection of naloxone, an opioid receptor antagonist, did not affect antinociception produced by intraperitoneal injections of both vitamin E and lidocaine. These results suggest that treatment with vitamin E enhances the systemic treatment with lidocaine-induced antinociception and reduces side effects when systemically treated with lidocaine. Therefore, the combined treatment with vitamin E and lidocaine is a potential therapeutic for chronic orofacial pain.
Administration, Intravenous ; Animals ; Facial Pain ; Formaldehyde ; Humans ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Lidocaine* ; Male ; Naloxone ; Rats* ; Rats, Sprague-Dawley ; Receptors, Opioid ; Vitamin E* ; Vitamins*

BACKGROUND/AIMS: Transjugular Intrahepatic Portosystemic Shunt (TIPS) is commonly used in patients with variceal bleeding. However, this procedure is contraindicated in hepatocellular carcinoma patients with portal vein thrombosis. This study was done to evaluate the effect of TIPS in those patients with variceal bleeding. METHODS: Between 1997 and 2004, six hepatocellular carcinoma (HCC) patients with portal vein thrombosis were enrolled in this study due to their variceal bleeding. All the patients underwent TIPS placement to treat the variceal bleeding that had not responded to endoscopic treatment. Effective shunt creation was assessed by the decrease of the portal pressure gradient (less than 12 mmHg) or if good patency and flow were seen on a doppler examination. RESULTS: Shunts were successfully created in all the patients and the bleeding was immediately controlled in the active bleeding cases. The bleeding was caused by esophageal varices in one patient and, by gastric varices in five patients. The HCC types were diffuse or massive in five patients, and a single nodule was present in one patient. All the patients had portal vein thrombosis. Rebleeding was noted in two patients at 10 days and 3 months, respectively, due to the shunt occlusion. Hepatic encephalopathy was noted in two patients. The causes of death were hepatorenal syndrome after 2 weeks in one patient, bleeding due to portal hypertensive gastropathy after 3 weeks in another, and cancer progression after 4 months in third patient. CONCLUSIONS: For HCC patients with portal vein thrombosis, TIPS can be an effective treatment modality if uncontrolled variceal bleeding presents when using endoscopic hemostasis or pharmacologic therapy. However, further studies are needed.
Adult ; Carcinoma, Hepatocellular/*complications ; English Abstract ; Esophageal and Gastric Varices/complications/*therapy ; Gastrointestinal Hemorrhage/*therapy ; Humans ; Liver Neoplasms/*complications ; Male ; Middle Aged ; *Portal Vein ; *Portasystemic Shunt, Transjugular Intrahepatic ; Venous Thrombosis/*complications