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Juliana Geremias Chichorro - One of the best experts on this subject based on the ideXlab platform.

  • vitamin b complex attenuated heat hyperalgesia following Infraorbital Nerve constriction in rats and reduced capsaicin in vivo and in vitro effects
    European Journal of Pharmacology, 2015
    Co-Authors: Caroline Machado Kopruszinski, Renata Cristiane Dos Reis, Elisangela Bressan, Peter W Reeh, Juliana Geremias Chichorro
    Abstract:

    Abstract Vitamins of the B complex attenuate some neuropathic pain sensory aspects in various animal models and in patients, but the mechanisms underlying their effects remain to be elucidated. Herein it was investigated if the treatment with a vitamin B complex (VBC) reduces heat hyperalgesia in rats submitted to Infraorbital Nerve constriction and the possibility that TRPV1 receptors represent a target for B vitamins. In the present study, the VBC refers to a combination of vitamins B1, B6 and B12 at low- (18, 18 and 1.8 mg/kg, respectively) or high- (180, 180 and 18 mg/kg, respectively) doses. Acute treatment of rats with either the low- or the high-doses combination reduced heat hyperalgesia after Nerve injury, but the high-doses combination resulted in a long-lasting effect. Repeated treatment with the low-dose combination reduced heat hyperalgesia on day four after Nerve injury and showed a synergist effect with a single injection of carbamazepine (3 or 10 mg/kg), which per se failed to modify the heat threshold. In naive rats, acute treatment with the high-dose of VBC or B1 and B12 vitamins independently reduced heat hyperalgesia evoked by capsaicin (3 µg into the upper lip). Moreover, the VBC, as well as, each one of the B vitamins independently reduced the capsaicin-induced calcium responses in HEK 293 cells transiently transfected with the human TRPV1 channels. Altogether, these results indicate that B vitamins can be useful to control heat hyperalgesia associated with trigeminal neuropathic pain and that modulation of TRPV1 receptors may contribute to their anti-hyperalgesic effects.

  • mechanisms operated by endothelin eta and etb receptors in the trigeminal ganglion contribute to orofacial thermal hyperalgesia induced by Infraorbital Nerve constriction in rats
    Neuropeptides, 2009
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Daniela Almeida Cabrini, Celia Regina Cavichiolo Franco, Giles A Rae
    Abstract:

    Abstract Endothelins, acting through specific endothelin ET A and/or ET B receptors, participate in nociceptive processing in models of cancer, inflammatory and neuropathic pain. The present study investigated which cell types express endothelin receptors in the trigeminal ganglion, and the contribution of mechanisms mediated by endothelin ET A and ET B receptors to orofacial heat hyperalgesia induced by unilateral constriction of the Infraorbital Nerve (CION). Both receptor types were identified by immunohistochemistry in the trigeminal ganglion, ET A receptors on small-sized non-myelinated and myelinated A-fibers and ET B receptors on both satellite glial cells and small-sized non-myelinated neuronal cells. CION promoted ipsilateral orofacial heat hyperalgesia which lasted from Day 2 until Day 10 after surgery. Ongoing CION-induced heat hyperalgesia (on Day 4) was reduced transiently, but significantly, by systemic or local treatment with antagonists of endothelin ET A receptors (atrasentan, 10mg/kg, i.v.; or BQ-123, 10nmol/lip), endothelin ET B receptors (A-192621, 20mg/kg, i.v.; or BQ-788, 10nmol/ lip), or of both ET A /ET B receptors (bosentan, 10mg/kg, i.v.; or BQ-123 plus BQ-788, each at 10nmol/lip). On the other hand, CION-induced heat hyperalgesia was transiently abolished over the first 90 min following i.p. injection of morphine hydrochloride (2.5mg/kg), but fully resistant to reversal by indomethacin (4mg/kg, i.p.) or celecoxib (10mg/kg, i.p.). Thus, heat hyperalgesia induced by CION is maintained, in part, by peripheral signaling mechanisms operated by ET A and ET B receptors. Endothelin receptors might represent promising therapeutic targets for the control of trigeminal neuropathic pain.

  • orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats reversal by endothelin receptor antagonists but not non steroidal anti inflammatory drugs
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    Abstract The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 μg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4 ± 1.3, carrageenan 21.2 ± 3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10 mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ETA or ETB receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3 ± 1.8, CION 32.4 ± 5.3 s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ETA (atrasentan, 3–10 mg/kg) or ETB (A-192621, 5–20 mg/kg) receptors caused significant inhibitions lasting 1–2.5 h (peaks ∼65–90%). Bosentan (dual ETA/ETB receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6 h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ETA and/or ETB receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

  • orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats reversal by endothelin receptor antagonists but not non steroidal anti inflammatory drugs
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    Abstract The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 μg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4 ± 1.3, carrageenan 21.2 ± 3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10 mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ETA or ETB receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3 ± 1.8, CION 32.4 ± 5.3 s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ETA (atrasentan, 3–10 mg/kg) or ETB (A-192621, 5–20 mg/kg) receptors caused significant inhibitions lasting 1–2.5 h (peaks ∼65–90%). Bosentan (dual ETA/ETB receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6 h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ETA and/or ETB receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

  • Orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats: reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs.
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 microg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4+/-1.3, carrageenan 21.2+/-3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3+/-1.8, CION 32.4+/-5.3s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ET(A) (atrasentan, 3-10 mg/kg) or ET(B) (A-192621, 5-20 mg/kg) receptors caused significant inhibitions lasting 1-2.5h (peaks approximately 65-90%). Bosentan (dual ET(A)/ET(B) receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ET(A) and/or ET(B) receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

Gloria E P Souza - One of the best experts on this subject based on the ideXlab platform.

  • orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats reversal by endothelin receptor antagonists but not non steroidal anti inflammatory drugs
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    Abstract The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 μg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4 ± 1.3, carrageenan 21.2 ± 3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10 mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ETA or ETB receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3 ± 1.8, CION 32.4 ± 5.3 s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ETA (atrasentan, 3–10 mg/kg) or ETB (A-192621, 5–20 mg/kg) receptors caused significant inhibitions lasting 1–2.5 h (peaks ∼65–90%). Bosentan (dual ETA/ETB receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6 h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ETA and/or ETB receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

  • orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats reversal by endothelin receptor antagonists but not non steroidal anti inflammatory drugs
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    Abstract The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 μg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4 ± 1.3, carrageenan 21.2 ± 3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10 mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ETA or ETB receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3 ± 1.8, CION 32.4 ± 5.3 s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ETA (atrasentan, 3–10 mg/kg) or ETB (A-192621, 5–20 mg/kg) receptors caused significant inhibitions lasting 1–2.5 h (peaks ∼65–90%). Bosentan (dual ETA/ETB receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6 h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ETA and/or ETB receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

  • Orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats: reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs.
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 microg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4+/-1.3, carrageenan 21.2+/-3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3+/-1.8, CION 32.4+/-5.3s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ET(A) (atrasentan, 3-10 mg/kg) or ET(B) (A-192621, 5-20 mg/kg) receptors caused significant inhibitions lasting 1-2.5h (peaks approximately 65-90%). Bosentan (dual ET(A)/ET(B) receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ET(A) and/or ET(B) receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

Barry J Sessle - One of the best experts on this subject based on the ideXlab platform.

  • α bisabolol reduces nociception and trigeminal central sensitisation in acute orofacial neuropathic pain induced by Infraorbital Nerve injury
    Life Sciences, 2019
    Co-Authors: L T Melo, V Panchalingam, P Cherkas, Adriana Rolim Campos, L Aviviarber, Barry J Sessle
    Abstract:

    Abstract Neuropathic orofacial pain conditions represent a challenge to diagnose and treat. Natural substances are promising therapeutic options for the control of pain. Aims This study aimed to examine whether (−)-α-bisabolol (BISA), a natural terpene, can attenuate nociceptive behaviour and central sensitisation in a rodent model of trigeminal neuropathic pain. Materials and methods Infraorbital Nerve transection (IONX) or sham operation was performed in adult male rats. Head withdrawal thresholds as a measure of facial mechanical sensitivity were tested with von Frey monofilaments applied bilaterally to the facial vibrissal pad pre-operatively (baseline) and then post-operatively before and at 60, 120, 240 and 360 min after administration of vehicle control per oris (p.o.) or BISA (200 mg/kg p.o.) (n = 8/group). Effects of BISA or vehicle on the activity of nociceptive neurons recorded in the medullary dorsal horn (MDH) were tested on post - operative day 8–10. ANOVA followed by post-hoc Bonferroni tested for statistically significant differences (p  Key findings IONX animals (but not sham or naive animals) showed post-operative facial mechanical hypersensitivity that was unaffected by vehicle. However, administration of BISA at post-operative day 7 significantly reversed the mechanical hypersensitivity in IONX rats; this effect lasted for at least 6 h. BISA also attenuated IONX-induced central sensitisation of MDH nociceptive neurons, as reflected in reversal of their reduced activation thresholds, increased responses to graded mechanical stimuli and enhanced spontaneous activity. Significance BISA may attenuate nociceptive behaviour and central sensitisation in a rat model of acute trigeminal neuropathic pain.

  • Involvement of ERK Phosphorylation of Trigeminal Spinal Subnucleus Caudalis Neurons in Thermal Hypersensitivity in Rats with Infraorbital Nerve Injury
    2016
    Co-Authors: Ikuko Suzuki, Kuniya Honda, Masamichi Shinoda, Yoshiyuki Tsuboi, Kazuo Shibuta, Ayano Katagiri, Masaaki Kiyomoto, Barry J Sessle, Shingo Matsuura, Kinuyo Ohara
    Abstract:

    To evaluate the involvement of the mitogen-activated protein kinase (MAPK) cascade in orofacial neuropathic pain mechanisms, this study assessed nocifensive behavior evoked by mechanical or thermal stimulation of the whisker pad skin, phosphorylation of extracellular signal-regulated kinase (ERK) in trigeminal spinal subnucleus caudalis (Vc) neurons, and Vc neuronal responses to mechanical or thermal stimulation of the whisker pad skin in rats with the chronic constriction Nerve injury of the Infraorbital Nerve (ION-CCI). The mechanical and thermal nocifensive behavior was significantly enhanced on the side ipsilateral to the ION-CCI compared to the contralateral whisker pad or sham rats. ION-CCI rats had an increased number of phosphorylated ERK immunoreactive (pERK-IR) cells which also manifested NeuN-IR but not GFAP-IR and Iba1-IR, and were significantly more in ION-CCI rats compared with sham rats following noxious but not non-noxious mechanical stimulation. After intrathecal administration of the MEK1 inhibitor PD98059 in ION-CCI rats, the number of pERK-IR cells after noxious stimulation and the enhanced thermal nocifensive behavior but not the mechanical nocifensive behavior were significantly reduced in ION-CCI rats. The enhanced background activities, afterdischarges and responses of wide dynami

  • the gap junction blocker carbenoxolone attenuates nociceptive behavior and medullary dorsal horn central sensitization induced by partial Infraorbital Nerve transection in rats
    Pain, 2014
    Co-Authors: Hua Wang, Chen Yu Chiang, Jonathan O Dostrovsky, Barry J Sessle
    Abstract:

    Abstract Glial cells are being increasingly implicated in mechanisms underlying pathological pain, and recent studies suggest glial gap junctions involving astrocytes may contribute. The aim of this study was to examine the effect of a gap junction blocker, carbenoxolone (CBX), on medullary dorsal horn (MDH) nociceptive neuronal properties and facial mechanical nociceptive behavior in a rat trigeminal neuropathic pain model involving partial transection of the Infraorbital Nerve (p-IONX). p-IONX produced facial mechanical hypersensitivity reflected in significantly reduced head withdrawal thresholds that lasted for more than 3 weeks. p-IONX also produced central sensitization in MDH nociceptive neurons that was reflected in significantly increased receptive field size, reduction of mechanical activation threshold, and increases in noxious stimulation-evoked responses. Intrathecal CBX treatment significantly attenuated the p-IONX–induced mechanical hypersensitivity and the MDH central sensitization parameters, compared to intrathecal vehicle treatment. These results provide the first documentation that gap junctions may be critically involved in orofacial neuropathic pain mechanisms.

  • involvement of erk phosphorylation of trigeminal spinal subnucleus caudalis neurons in thermal hypersensitivity in rats with Infraorbital Nerve injury
    PLOS ONE, 2013
    Co-Authors: Ikuko Suzuki, Kuniya Honda, Masamichi Shinoda, Yoshiyuki Tsuboi, Kazuo Shibuta, Ayano Katagiri, Masaaki Kiyomoto, Barry J Sessle, Shingo Matsuura, Kinuyo Ohara
    Abstract:

    To evaluate the involvement of the mitogen-activated protein kinase (MAPK) cascade in orofacial neuropathic pain mechanisms, this study assessed nocifensive behavior evoked by mechanical or thermal stimulation of the whisker pad skin, phosphorylation of extracellular signal-regulated kinase (ERK) in trigeminal spinal subnucleus caudalis (Vc) neurons, and Vc neuronal responses to mechanical or thermal stimulation of the whisker pad skin in rats with the chronic constriction Nerve injury of the Infraorbital Nerve (ION-CCI). The mechanical and thermal nocifensive behavior was significantly enhanced on the side ipsilateral to the ION-CCI compared to the contralateral whisker pad or sham rats. ION-CCI rats had an increased number of phosphorylated ERK immunoreactive (pERK-IR) cells which also manifested NeuN-IR but not GFAP-IR and Iba1-IR, and were significantly more in ION-CCI rats compared with sham rats following noxious but not non-noxious mechanical stimulation. After intrathecal administration of the MEK1 inhibitor PD98059 in ION-CCI rats, the number of pERK-IR cells after noxious stimulation and the enhanced thermal nocifensive behavior but not the mechanical nocifensive behavior were significantly reduced in ION-CCI rats. The enhanced background activities, afterdischarges and responses of wide dynamic range neurons to noxious mechanical and thermal stimulation in ION-CCI rats were significantly depressed following i.t. administration of PD98059, whereas responses to non-noxious mechanical and thermal stimulation were not altered. The present findings suggest that pERK-IR neurons in the Vc play a pivotal role in the development of thermal hypersensitivity in the face following trigeminal Nerve injury.

Aleksander R Zampronio - One of the best experts on this subject based on the ideXlab platform.

  • mechanisms operated by endothelin eta and etb receptors in the trigeminal ganglion contribute to orofacial thermal hyperalgesia induced by Infraorbital Nerve constriction in rats
    Neuropeptides, 2009
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Daniela Almeida Cabrini, Celia Regina Cavichiolo Franco, Giles A Rae
    Abstract:

    Abstract Endothelins, acting through specific endothelin ET A and/or ET B receptors, participate in nociceptive processing in models of cancer, inflammatory and neuropathic pain. The present study investigated which cell types express endothelin receptors in the trigeminal ganglion, and the contribution of mechanisms mediated by endothelin ET A and ET B receptors to orofacial heat hyperalgesia induced by unilateral constriction of the Infraorbital Nerve (CION). Both receptor types were identified by immunohistochemistry in the trigeminal ganglion, ET A receptors on small-sized non-myelinated and myelinated A-fibers and ET B receptors on both satellite glial cells and small-sized non-myelinated neuronal cells. CION promoted ipsilateral orofacial heat hyperalgesia which lasted from Day 2 until Day 10 after surgery. Ongoing CION-induced heat hyperalgesia (on Day 4) was reduced transiently, but significantly, by systemic or local treatment with antagonists of endothelin ET A receptors (atrasentan, 10mg/kg, i.v.; or BQ-123, 10nmol/lip), endothelin ET B receptors (A-192621, 20mg/kg, i.v.; or BQ-788, 10nmol/ lip), or of both ET A /ET B receptors (bosentan, 10mg/kg, i.v.; or BQ-123 plus BQ-788, each at 10nmol/lip). On the other hand, CION-induced heat hyperalgesia was transiently abolished over the first 90 min following i.p. injection of morphine hydrochloride (2.5mg/kg), but fully resistant to reversal by indomethacin (4mg/kg, i.p.) or celecoxib (10mg/kg, i.p.). Thus, heat hyperalgesia induced by CION is maintained, in part, by peripheral signaling mechanisms operated by ET A and ET B receptors. Endothelin receptors might represent promising therapeutic targets for the control of trigeminal neuropathic pain.

  • orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats reversal by endothelin receptor antagonists but not non steroidal anti inflammatory drugs
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    Abstract The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 μg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4 ± 1.3, carrageenan 21.2 ± 3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10 mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ETA or ETB receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3 ± 1.8, CION 32.4 ± 5.3 s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ETA (atrasentan, 3–10 mg/kg) or ETB (A-192621, 5–20 mg/kg) receptors caused significant inhibitions lasting 1–2.5 h (peaks ∼65–90%). Bosentan (dual ETA/ETB receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6 h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ETA and/or ETB receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

  • orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats reversal by endothelin receptor antagonists but not non steroidal anti inflammatory drugs
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    Abstract The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 μg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4 ± 1.3, carrageenan 21.2 ± 3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10 mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ETA or ETB receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3 ± 1.8, CION 32.4 ± 5.3 s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ETA (atrasentan, 3–10 mg/kg) or ETB (A-192621, 5–20 mg/kg) receptors caused significant inhibitions lasting 1–2.5 h (peaks ∼65–90%). Bosentan (dual ETA/ETB receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6 h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ETA and/or ETB receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

  • Orofacial cold hyperalgesia due to Infraorbital Nerve constriction injury in rats: reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs.
    Pain, 2006
    Co-Authors: Juliana Geremias Chichorro, Aleksander R Zampronio, Gloria E P Souza
    Abstract:

    The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the Infraorbital Nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 microg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4+/-1.3, carrageenan 21.2+/-3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3+/-1.8, CION 32.4+/-5.3s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ET(A) (atrasentan, 3-10 mg/kg) or ET(B) (A-192621, 5-20 mg/kg) receptors caused significant inhibitions lasting 1-2.5h (peaks approximately 65-90%). Bosentan (dual ET(A)/ET(B) receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ET(A) and/or ET(B) receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

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  • real time ultrasound guided Infraorbital Nerve block to treat trigeminal neuralgia using a high concentration of tetracaine dissolved in bupivacaine
    Scandinavian Journal of Pain, 2015
    Co-Authors: Kenichi Takechi, Amane Konishi, Kotaro Kikuchi, Shiho Fujioka, Tomomi Fujii, Toshihiro Yorozuya, K Kuzume, Takumi Nagaro
    Abstract:

    Abstract Background Trigeminal neuralgia is a neuropathic disorder characterized by episodes of intense pain in the face. Drug therapy is the first choice of treatment. However, in cases where drug therapy are contraindicated due to side effects, patients can get pain relief from lengthy neurosurgical procedures. Alternatively, a peripheral trigeminal Nerve block can be easily performed in an outpatient setting. Therefore it is a useful treatment option for the acute paroxysmal period of TN in patients who cannot use drug therapy. We performed real-time ultrasound guidance for Infraorbital Nerve blocks in TN patients using a high concentration of tetracaine dissolved in bupivacaine. In this report, we examine the efficacy of our methods. Patients : As approved by the Institutional Review Board, the medical records in our hospital were queried retrospectively. Six patients with TN at the V2 area matched the study criteria. All patients could not continue drug therapy with carbamazepine due to side effects and they received an ultrasound-guided Infraorbital Nerve block with a high concentration of tetracaine dissolved in bupivacaine. Methods The patient was placed in the supine position and the patient's face was sterilized and draped. An ultrasound system with a 6–13 MHz linear probe was used with a sterile cover. The probe was inserted into the horizontal plane of the cheek just beside the nose and was slid in the cranial direction to find the dimple of the Infraorbital foramen. The 25G 25 mm needle was inserted from the caudal side just across from the probe using an out-of-plane approach. To lead the needle tip to the foramen, needle direction was corrected with real-time ultrasound guidance. After the test block with lidocaine (2%, 0.5 ml), a solution of tetracaine (20 mg) dissolved in bupivacaine (0.5%, 0.5 ml) was injected. During each injection, the spread of the agent around the Nerve was confirmed using ultrasound images. Results Ten blocks were performed for six patients. Immediately after the procedure, all 10 blocks produced analgesia and relieved the pain. In the three blocks, pain was experienced in a new trigger point outside of the Infraorbital Nerve region (around the back teeth) within a week after the block and pain were relieved using other treatment. Two patients developed small hematomas in the cheek but they disappeared in a week. All patients did not complain about other side effects including paraesthesia, hyperpathia, dysaesthesia, or double vision. Hypoaesthesia to touch and pain in the Infraorbital region were observed in all blocks after 2 weeks. Conclusions We performed real-time ultrasound-guided Infraorbital Nerve block for TN with a high concentration of tetracaine dissolved in bupivacaine. Our method achieved a high success rate and there were only minor and transient side effects. Implications : Real-time ultrasound-guided Infraorbital Nerve block is one of the useful options to treat the acute paroxysmal period of TN at the Infraorbital Nerve area. Ultrasound-guided injections may become the standard practice for injecting peripheral trigeminal Nerves. Using this high concentration of tetracaine as a neurolytic agent is effective and appears to have only minor side effects.