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(119) A Comparative Study on the Sedative Effect of Oral Midazolam and oral Promethazine Medication in lumbar puncture
S6
Abstracts
The Journal of Pain
Trigeminal nerves innervating the orofacial region express the nociceptive transient receptor potential vanilloid-1 (TRPV1) ion channel. TRPV1 activation results in calcium influx and post-synaptic release of proinflammatory mediators, such as calcitonin-gene related peptide (CGRP). The neurotransmitter serotonin (5-hydroxytryptamine, 5HT) also acts as a proinflammatory and pronociceptive mediator in the periphery. 5HT can alter sensory thresholds by binding excitatory 5HT receptors, such as 5HT2A, which may sensitize TRPV1. Previous studies reported that 5HT receptors co-localize with TRPV1 and can potentiate TRPV1 activity. These studies were done in males; however, pain conditions that activate trigeminal neurons are more prevalent in females. This sexual dimorphism may be attributed to fluctuating hormone levels, which may influence the peripheral serotonin system. We hypothesized that 17b-estradiol (E2) acts through membrane bound receptors to rapidly enhance 5HT potentiation of CGRP release from the TRPV1 population of trigeminal sensory neurons. Primary neuronal cultures from ovariectomized adult female rats were pre-treated with E2, 5HT, or a combination prior to stimulation with capsaicin (TRPV1 agonist). CGRP release after each treatment was quantitated by ELISA. Our data shows that capsaicin-evoked CGRP release was significantly increased following pre-treatment with 5HT and E2 compared to vehicle. Cells were also treated with a membrane-impermeable E2 (E2-BSA) to differentiate between action at the membrane bound receptor or a genomic receptor. Our preliminary data indicate that E2-BSA did not enhance serotonergic potentiation of capsaicin-evoked CGRP release, indicating rapid action through an internal receptor may be involved. Our data indicates that sex differences in trigeminal pain disorders may be, in part, due to estrous cycle-dependent plasticity in the enhancing effects of E2 on the 5HT-TRPV1 pain mechanism. We are currently analyzing the expression of 5HT2A receptors, E2 receptors, and TRPV1 ion channels across the estrous cycle to detect potential plasticity. Supported by a TWU Research Enhancement Grant.
study, we employed optogenetic and chemogenetic manipulation approaches to investigate the role of the dopaminergic pathway from hypothalamic A11 nucleus to trigeminal nucleus caudalis (TNC) in orofacial neuropathic pain. Dopamine receptor D1-Cre male mice were used in this study. A chronic constriction injury-infraorbital nerve (CCI-ION) mouse model was prepared as described previously. Optogenetic and chemogenetic experiments were conducted to examine the effect of activation or inhibition of D1-mediated dopaminergic signaling on orofacial neuropathic pain in the CCI-ION model. Conditional place preference (CPP) was used to measure the emotional component of pain behaviors in freely moving mice. Immunohistochemistry staining was used to assess the expression of D1 receptor, dopamine reuptake transporter (DAT) and tyrosine hydroxylase (TH). CPP testing showed that D1-Cre mice injected with the inhibitory virus AAV5-EF1a-DIO-eNpHR3.0-EYFP exhibited a decrease in pain behaviors when stimulated with green light (532 nm), but D1-Cre mice injected with the excitatory virus AAV5EF1a-DIO-ChR2 (E123A)-EYFP exhibited an increase in pain behaviors when stimulated with blue light (473 nm). Moreover, D1-Cre mice injected with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)-based excitatory virus AAV5-hSyn-DIOhM3D(Gq)-mCherry showed significantly increased pain behaviors following clozapine N-oxide i.p. injection. 6-hydroxy-dopamine hydrobromide (6-OHDA)-produced specific lesion blocked the effects of both optogenetic and chemogenetic manipulation on orofacial neuropathic pain in this CCI-ION model. In addition, D1 receptor was highly expressed in the TNC, and DAT and TH were expressed in the TNC and the A11 nucleus, respectively. The descending dopaminergic pathway from A11 to TNC could be a critical target for the treatment of orofacial neuropathic pain. Supported by NIH/NIDCR Grants R01 DE022880 and K02 DE023551.
(117) Lipopolysaccharide but not lipoteichoic acid induces inflammation and sensitization of nerve ending in the dental pulp
H Derakhshanfar; Mofid Children Hospital, Tehran, Iran
B Michot, S Casey, M Jain, A Kim, A Ramsey, and J Gibbs; NYU College of Dentistry, New York, NY
Painful pulpitis is an inflammation of the dental pulp caused by bacterial proliferation near the pulp after tooth damage or caries. Previous data show that toxins produced by bacteria are particularly important in the induction of inflammation, and the toxin lipopolysaccharide can directly activate sensory neurons. In this study we evaluated the effects of the bacterial toxins lipopolysaccharide (LPS) from E. coli and lipoteichoic acid (LTA) from Bacillus subtilis on neuronal sensitization and cytokine production in an ex vivo model using human tooth slices. Healthy 3rd molars were collected and sectioned to obtain 2-3 slices, 1mm thick, per tooth. Tooth slices were treated with either LPS (1 and 100ug/ml), LTA (1 and 100ug/ml) or control media culture for 3 or 24h. After incubation with LPS or vehicle, calcitonin gene related peptide (CGRP) release from peripheral sensory nerve endings was stimulated with capsaicin (6 mM), and the supernatent was collected, concentrated and CGRP was quantified by ELISA. The release of the cytokines (IFNg, IL10, IL12p70, IL13, IL1b IL2, IL4, IL6, IL8 and TNFa) in the culture media was quantified with an MSD multiplex assay kit. Although 3h treatment with LPS did not induce changes in CGRP or cytokine release compared to control tooth slices, 24h treatment with LPS (100mg/ ml) increased the release of CGRP from sensory nerve endings, pro-inflammatory cytokines, IFNg, IL1b and TNFa and the anti-inflammatory cytokine IL10 from the dental pulp. In contrast, 24h treatment with LTA (1 and 100 mg/ml) did not affect the level of CGRP or cytokine release compared to control tooth slices. In conclusion, LPS is a more important toxin than LTA in producing neuronal sensitization and inflammation that contribute to painful pulpitis.
(118) Role of descending dopaminergic signaling in orofacial neuropathic pain S Liu, D Taturn, Y Tang, H Shu, Q Bai, and F Tao; Texas A&M Health Science Center, Bryan, TX
Orofacial neuropathic pain is a debilitating condition and represents a challenge to clinicians since the mechanisms underlying orofacial neuropathic pain are not fully understood. In the present
(119) A Comparative Study on the Sedative Effect of Oral Midazolam and oral Promethazine Medication in lumbar puncture Lumbar puncture (LP) essentially is a painful and stressful procedure that indicated for diagnosis and therapeutic purposes. One way to reduce the anxiety is oral premedication. The aim of this study is to compare clinical effects of oral Midazolam and oral Promethazine. This prospective randomized controlled clinical trial study was performed on 80 children 2-7 years old were candidate for LP. They were divided into two randomized equal groups. First group received oral Midazolam syrp 0.5 mg/kg and the other group received oral Promethazine syrp 1 mg/kg. Level of sedation, hemodynamic changes and any other complications monitored every 5 minutes from 30 minutes before the start of the procedure. Midazolam group and Promethazine group were similar in age, gender and weight. Oral Midazolam significantly had shorter onset of sedation (P<0.001) and also shorter duration to maximal sedation (P<0.022). The two groups were similar with respect to sedative effect at all time. The only complication that was significantly more in Midazolam group, nausea and vomiting (P<0.012). Midazolam syrp and Promethazine syrp have same sedative effect in children. Both of these medications are easy to use in preschool children and none of them appeared to be superior to another.
Diet (120) Diet and bioactive lipid mediators for treatment of chronic pain: a translational approach A Domenichiello, B Wilhite, M Pitcher, C Bushnell, and C Ramsden; National Institutes of Health, Bethesda, MD As key components of cellular membranes, fatty acids and their bioactive lipid mediator derivatives are uniquely positioned to impact chronic pain. A small clinical trial performed in our laboratory found that increasing omega-3 (n-3) PUFA and decreasing omega-6 (n-6) PUFA (H3L6 diet) caused decreases in headaches and improvements in quality of life in chronic daily headache sufferers.1 These clinical improvements were accompanied by increases in anti-nociceptive and pro-resolving n-3 derived lipid mediators, and reductions in pro-nociceptive n-6 derived mediators in plasma. However, the effects of the H3-L6 diet on these lipid mediators in tissues that are more directly implicated in the pathogenesis of chronic pain are presently
Abstracts
The Journal of Pain
Trigeminal nerves innervating the orofacial region express the nociceptive transient receptor potential vanilloid-1 (TRPV1) ion channel. TRPV1 activation results in calcium influx and post-synaptic release of proinflammatory mediators, such as calcitonin-gene related peptide (CGRP). The neurotransmitter serotonin (5-hydroxytryptamine, 5HT) also acts as a proinflammatory and pronociceptive mediator in the periphery. 5HT can alter sensory thresholds by binding excitatory 5HT receptors, such as 5HT2A, which may sensitize TRPV1. Previous studies reported that 5HT receptors co-localize with TRPV1 and can potentiate TRPV1 activity. These studies were done in males; however, pain conditions that activate trigeminal neurons are more prevalent in females. This sexual dimorphism may be attributed to fluctuating hormone levels, which may influence the peripheral serotonin system. We hypothesized that 17b-estradiol (E2) acts through membrane bound receptors to rapidly enhance 5HT potentiation of CGRP release from the TRPV1 population of trigeminal sensory neurons. Primary neuronal cultures from ovariectomized adult female rats were pre-treated with E2, 5HT, or a combination prior to stimulation with capsaicin (TRPV1 agonist). CGRP release after each treatment was quantitated by ELISA. Our data shows that capsaicin-evoked CGRP release was significantly increased following pre-treatment with 5HT and E2 compared to vehicle. Cells were also treated with a membrane-impermeable E2 (E2-BSA) to differentiate between action at the membrane bound receptor or a genomic receptor. Our preliminary data indicate that E2-BSA did not enhance serotonergic potentiation of capsaicin-evoked CGRP release, indicating rapid action through an internal receptor may be involved. Our data indicates that sex differences in trigeminal pain disorders may be, in part, due to estrous cycle-dependent plasticity in the enhancing effects of E2 on the 5HT-TRPV1 pain mechanism. We are currently analyzing the expression of 5HT2A receptors, E2 receptors, and TRPV1 ion channels across the estrous cycle to detect potential plasticity. Supported by a TWU Research Enhancement Grant.
study, we employed optogenetic and chemogenetic manipulation approaches to investigate the role of the dopaminergic pathway from hypothalamic A11 nucleus to trigeminal nucleus caudalis (TNC) in orofacial neuropathic pain. Dopamine receptor D1-Cre male mice were used in this study. A chronic constriction injury-infraorbital nerve (CCI-ION) mouse model was prepared as described previously. Optogenetic and chemogenetic experiments were conducted to examine the effect of activation or inhibition of D1-mediated dopaminergic signaling on orofacial neuropathic pain in the CCI-ION model. Conditional place preference (CPP) was used to measure the emotional component of pain behaviors in freely moving mice. Immunohistochemistry staining was used to assess the expression of D1 receptor, dopamine reuptake transporter (DAT) and tyrosine hydroxylase (TH). CPP testing showed that D1-Cre mice injected with the inhibitory virus AAV5-EF1a-DIO-eNpHR3.0-EYFP exhibited a decrease in pain behaviors when stimulated with green light (532 nm), but D1-Cre mice injected with the excitatory virus AAV5EF1a-DIO-ChR2 (E123A)-EYFP exhibited an increase in pain behaviors when stimulated with blue light (473 nm). Moreover, D1-Cre mice injected with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)-based excitatory virus AAV5-hSyn-DIOhM3D(Gq)-mCherry showed significantly increased pain behaviors following clozapine N-oxide i.p. injection. 6-hydroxy-dopamine hydrobromide (6-OHDA)-produced specific lesion blocked the effects of both optogenetic and chemogenetic manipulation on orofacial neuropathic pain in this CCI-ION model. In addition, D1 receptor was highly expressed in the TNC, and DAT and TH were expressed in the TNC and the A11 nucleus, respectively. The descending dopaminergic pathway from A11 to TNC could be a critical target for the treatment of orofacial neuropathic pain. Supported by NIH/NIDCR Grants R01 DE022880 and K02 DE023551.
(117) Lipopolysaccharide but not lipoteichoic acid induces inflammation and sensitization of nerve ending in the dental pulp
H Derakhshanfar; Mofid Children Hospital, Tehran, Iran
B Michot, S Casey, M Jain, A Kim, A Ramsey, and J Gibbs; NYU College of Dentistry, New York, NY
Painful pulpitis is an inflammation of the dental pulp caused by bacterial proliferation near the pulp after tooth damage or caries. Previous data show that toxins produced by bacteria are particularly important in the induction of inflammation, and the toxin lipopolysaccharide can directly activate sensory neurons. In this study we evaluated the effects of the bacterial toxins lipopolysaccharide (LPS) from E. coli and lipoteichoic acid (LTA) from Bacillus subtilis on neuronal sensitization and cytokine production in an ex vivo model using human tooth slices. Healthy 3rd molars were collected and sectioned to obtain 2-3 slices, 1mm thick, per tooth. Tooth slices were treated with either LPS (1 and 100ug/ml), LTA (1 and 100ug/ml) or control media culture for 3 or 24h. After incubation with LPS or vehicle, calcitonin gene related peptide (CGRP) release from peripheral sensory nerve endings was stimulated with capsaicin (6 mM), and the supernatent was collected, concentrated and CGRP was quantified by ELISA. The release of the cytokines (IFNg, IL10, IL12p70, IL13, IL1b IL2, IL4, IL6, IL8 and TNFa) in the culture media was quantified with an MSD multiplex assay kit. Although 3h treatment with LPS did not induce changes in CGRP or cytokine release compared to control tooth slices, 24h treatment with LPS (100mg/ ml) increased the release of CGRP from sensory nerve endings, pro-inflammatory cytokines, IFNg, IL1b and TNFa and the anti-inflammatory cytokine IL10 from the dental pulp. In contrast, 24h treatment with LTA (1 and 100 mg/ml) did not affect the level of CGRP or cytokine release compared to control tooth slices. In conclusion, LPS is a more important toxin than LTA in producing neuronal sensitization and inflammation that contribute to painful pulpitis.
(118) Role of descending dopaminergic signaling in orofacial neuropathic pain S Liu, D Taturn, Y Tang, H Shu, Q Bai, and F Tao; Texas A&M Health Science Center, Bryan, TX
Orofacial neuropathic pain is a debilitating condition and represents a challenge to clinicians since the mechanisms underlying orofacial neuropathic pain are not fully understood. In the present
(119) A Comparative Study on the Sedative Effect of Oral Midazolam and oral Promethazine Medication in lumbar puncture Lumbar puncture (LP) essentially is a painful and stressful procedure that indicated for diagnosis and therapeutic purposes. One way to reduce the anxiety is oral premedication. The aim of this study is to compare clinical effects of oral Midazolam and oral Promethazine. This prospective randomized controlled clinical trial study was performed on 80 children 2-7 years old were candidate for LP. They were divided into two randomized equal groups. First group received oral Midazolam syrp 0.5 mg/kg and the other group received oral Promethazine syrp 1 mg/kg. Level of sedation, hemodynamic changes and any other complications monitored every 5 minutes from 30 minutes before the start of the procedure. Midazolam group and Promethazine group were similar in age, gender and weight. Oral Midazolam significantly had shorter onset of sedation (P<0.001) and also shorter duration to maximal sedation (P<0.022). The two groups were similar with respect to sedative effect at all time. The only complication that was significantly more in Midazolam group, nausea and vomiting (P<0.012). Midazolam syrp and Promethazine syrp have same sedative effect in children. Both of these medications are easy to use in preschool children and none of them appeared to be superior to another.
Diet (120) Diet and bioactive lipid mediators for treatment of chronic pain: a translational approach A Domenichiello, B Wilhite, M Pitcher, C Bushnell, and C Ramsden; National Institutes of Health, Bethesda, MD As key components of cellular membranes, fatty acids and their bioactive lipid mediator derivatives are uniquely positioned to impact chronic pain. A small clinical trial performed in our laboratory found that increasing omega-3 (n-3) PUFA and decreasing omega-6 (n-6) PUFA (H3L6 diet) caused decreases in headaches and improvements in quality of life in chronic daily headache sufferers.1 These clinical improvements were accompanied by increases in anti-nociceptive and pro-resolving n-3 derived lipid mediators, and reductions in pro-nociceptive n-6 derived mediators in plasma. However, the effects of the H3-L6 diet on these lipid mediators in tissues that are more directly implicated in the pathogenesis of chronic pain are presently