- Email: [email protected]
(673)
Abstracts
B13 - Opioid Action (669) Regulation of vascular permeability via Mu receptors R Puana, J Bean-Lijewski, R McAllister, J Warden, E Childs; Scott and White Memorial Hospital, Texas A&M University, Temple, TX Hemorrhage is associated with an increase in permeability resulting in decreased preload and increased tissue edema. Morphine sulfate is frequently administered as an analgesic or anxiolytic in multi-injured patients. Morphine binds to the Mu receptors located on the surface of endothelial cells and could theoretically augment the hyperpermeable state by histamine release. A recent study from our laboratory demonstrated that morphine inhibited the anticipated increase of vascular permeability in endothelial cells following hemorrhagic shock in rats. The aim of this study is to identify the pathway whereby this inhibition occurs. It is hypothesized that adenylate cyclase is upregulated through Mu receptor activation that inhibits the phosphoinositol/MAP kinase hyperpermeability cascade following hemmorhagic shock. Pilot studies were conducted in urethrane anesthetized Sprague Dawley rats. Initial studies determined the ED50 and LD50 for adenylate cyclase inhibitor (ACI) (sq22536). Six urethrane anesthetized Sprague Dawley rats were instrumented and permitted to recover for 15 minutes. Fluorescein isothiocyanate-bovine albumin (FITC-albumin), 50mg/ kg, was administered intravenously after which baseline intra- and extralumenal fluorescent light intensity was measured in mesenteric postcapillary venules of transilluminated segments of small intestine. ACI, 100 mcg/kg, was subsequently administered and identical mesenteric postcapillary venules were examined to quantitate changes in permeability. The fluorescent light intensity emitted from the FITC-albumin was recorded at baseline and at 5-minute intervals for four measures and 10-minute intervals for 120 minutes after ACI administration. These images were downloaded to a computerized image analysis program that quantitates changes in light intensity. The ratio of intralumenal: extralumenal light intensity represents changes in vascular permeability. In the absence of shock, ACI administration resulted in significant decrease in light intensity ratio representing profound increase in permeability. Preliminary data suggest that this increase is attenuated by morphine administration supporting the hypothesis that morphine inhibits the phosphoinositol/MAP kinase hyperpermeability via adenylate cyclase activation.
B14 - Pain Pathways (670) Prolactin regulation of trigeminal sensory neurons A Diogenes; University of Texas Health Science Center at San Antonio, San Antonio, TX Society for Neuroscience abstract
(671) Cannabinoids inhibit Capsaicin-sensitive neurons via heterologous desensitization mediated by the TRPA1/ TRPV1 heteromers NR Ruparel; University of Texas Health Science Center at San Antonio, San Antonio, TX Society for Neuroscience abstract
(672) Involvement of the calcium-calcineurin pathway in peripheral cannabinoid-induced antihyperalgesia/antinociception AM Patwardhan; University of Texas Health Science Center at San Antonio, San Antonio, TX Society for Neuroscience abstract
S23 (673) Modulation of peripheral trigeminal nociceptors by beta adrenergic receptor-1 J Vela, A Akopian, K Hargreaves; Univ of Texas Health Science Center, San Antonio, TX In this study we characterized the expression of the beta adrenergic receptors ( ⫺AR) in the trigeminal ganglia, as well as  receptor colocalization with Transient Receptor Potential Vanilloid 1 (TRPV1), a marker of nociceptive neurons. We further employed anatomical and biochemical methods to test the hypothesis that  ⫺AR1activation can modulate peripheral nociceptors under either basal or conditions that mimic inflammation. Rat trigeminal ganglia were harvested and prepared for combined in situ hybridization, and immunohistochemistry of the  ⫺AR1. Functional assays used primary rat trigeminal cultures and evaluated  ⫺AR modulation of iCGRP release (measured by RIA) and changes in intracellular calcium ([Ca]i; assessed by changes in fura-2 fluorescence). Data were analyzed by ANOVA. The anatomical expression studies indicate that the  ⫺AR1 is present in 39.7% of trigeminal neurons, and importantly, exhibits a 65.2% co-expression with TRPV1, a marker for a major subset of trigeminal nociceptors. Pretreatment with denopamine, a  ⫺AR1 agonist, had no effect on bradykinin-evoked release of iCGRP or [Ca]i levels under basal conditions. However, previous studies have demonstrated that BK primes GPCR signaling in trigeminal neurons (Patwardhan et al., J Neuroscience 2005). Therefore, we pre-treated cultures with BK (10 uM) and observed the development of a rapid (⬍10min), significant (p⬍0.01) and concentration-dependent denopamine inhibition of both BK-evoked CGRP release and changes in [Ca]i. Collectively, these preliminary studies are consistent with the hypothesis that activation of the  adrenergic receptor inhibits trigeminal nociceptors under prior conditions that involve release of the inflammatory mediator bradykinin. This work further suggests the prospect of utilizing the  adrenergics in the treatment of pain. Supported in part by F30 DE017307.
(674) Seeing the world through the lens of pain: Does chronic lower body pain compress visual perception of distance? J Augustyn, A Cook, P Brawer; The Miriam Hospital/Brown Medical School, Providence, RI Chronic pain has profound effects across a broad spectrum of biopsychosocial variables, including affective state, motor function, sleep, and the maintenance of meaningful social relationships. It commonly affects individuals’ interactions with their physical environments through psychological variables such as pain-related fear, disability perception, and avoidance behaviors. This pilot study examined whether chronic pain also influences a more fundamental neurocognitive process: the visual perception of distance. We compared distance perception in 49 patients (63.3% female; mean age 46.63 yrs, SD ⫽ 10.27) undergoing evaluation for treatment at a multidisciplinary pain management clinic and 49 healthy controls (65.3% female; mean age 41.13 yrs, SD ⫽ 11.13). All patients reported low back and/or lower extremity pain as their primary pain condition. Average duration of chronic pain was 7.71 years (SD ⫽ 7.38). Both patients and controls were asked to estimate the distance from their point of view to a target placed 13.4 meters (44 feet) away in a hallway. Patients underestimated distance (M ⫽ 10.63 m, SD ⫽ 3.83) relative to controls (M ⫽ 12.06 m, SD ⫽ 4.06); this difference approached significance (p ⫽ .07). Distance estimates were weakly correlated with self-report ratings of pain duration (r ⫽ .22), positive affect (r ⫽ .17), CRPP pain beliefs (r ⫽ ⫺.25), and TSK fear of movement scores (r ⫽ .18). These preliminary findings are consistent with an emerging view in cognitive science that visual perception is informed by the physical state of the body and suggest that pain sufferers may literally see the world differently than non-sufferers do. Effects of chronic pain on visual perception have theoretical significance for understanding how pain impacts functionality (e.g., walking, driving). Such effects may also have clinical significance as measures of pain impact and therapeutic progression and as potential targets for neurocognitive remediation interventions.
B13 - Opioid Action (669) Regulation of vascular permeability via Mu receptors R Puana, J Bean-Lijewski, R McAllister, J Warden, E Childs; Scott and White Memorial Hospital, Texas A&M University, Temple, TX Hemorrhage is associated with an increase in permeability resulting in decreased preload and increased tissue edema. Morphine sulfate is frequently administered as an analgesic or anxiolytic in multi-injured patients. Morphine binds to the Mu receptors located on the surface of endothelial cells and could theoretically augment the hyperpermeable state by histamine release. A recent study from our laboratory demonstrated that morphine inhibited the anticipated increase of vascular permeability in endothelial cells following hemorrhagic shock in rats. The aim of this study is to identify the pathway whereby this inhibition occurs. It is hypothesized that adenylate cyclase is upregulated through Mu receptor activation that inhibits the phosphoinositol/MAP kinase hyperpermeability cascade following hemmorhagic shock. Pilot studies were conducted in urethrane anesthetized Sprague Dawley rats. Initial studies determined the ED50 and LD50 for adenylate cyclase inhibitor (ACI) (sq22536). Six urethrane anesthetized Sprague Dawley rats were instrumented and permitted to recover for 15 minutes. Fluorescein isothiocyanate-bovine albumin (FITC-albumin), 50mg/ kg, was administered intravenously after which baseline intra- and extralumenal fluorescent light intensity was measured in mesenteric postcapillary venules of transilluminated segments of small intestine. ACI, 100 mcg/kg, was subsequently administered and identical mesenteric postcapillary venules were examined to quantitate changes in permeability. The fluorescent light intensity emitted from the FITC-albumin was recorded at baseline and at 5-minute intervals for four measures and 10-minute intervals for 120 minutes after ACI administration. These images were downloaded to a computerized image analysis program that quantitates changes in light intensity. The ratio of intralumenal: extralumenal light intensity represents changes in vascular permeability. In the absence of shock, ACI administration resulted in significant decrease in light intensity ratio representing profound increase in permeability. Preliminary data suggest that this increase is attenuated by morphine administration supporting the hypothesis that morphine inhibits the phosphoinositol/MAP kinase hyperpermeability via adenylate cyclase activation.
B14 - Pain Pathways (670) Prolactin regulation of trigeminal sensory neurons A Diogenes; University of Texas Health Science Center at San Antonio, San Antonio, TX Society for Neuroscience abstract
(671) Cannabinoids inhibit Capsaicin-sensitive neurons via heterologous desensitization mediated by the TRPA1/ TRPV1 heteromers NR Ruparel; University of Texas Health Science Center at San Antonio, San Antonio, TX Society for Neuroscience abstract
(672) Involvement of the calcium-calcineurin pathway in peripheral cannabinoid-induced antihyperalgesia/antinociception AM Patwardhan; University of Texas Health Science Center at San Antonio, San Antonio, TX Society for Neuroscience abstract
S23 (673) Modulation of peripheral trigeminal nociceptors by beta adrenergic receptor-1 J Vela, A Akopian, K Hargreaves; Univ of Texas Health Science Center, San Antonio, TX In this study we characterized the expression of the beta adrenergic receptors ( ⫺AR) in the trigeminal ganglia, as well as  receptor colocalization with Transient Receptor Potential Vanilloid 1 (TRPV1), a marker of nociceptive neurons. We further employed anatomical and biochemical methods to test the hypothesis that  ⫺AR1activation can modulate peripheral nociceptors under either basal or conditions that mimic inflammation. Rat trigeminal ganglia were harvested and prepared for combined in situ hybridization, and immunohistochemistry of the  ⫺AR1. Functional assays used primary rat trigeminal cultures and evaluated  ⫺AR modulation of iCGRP release (measured by RIA) and changes in intracellular calcium ([Ca]i; assessed by changes in fura-2 fluorescence). Data were analyzed by ANOVA. The anatomical expression studies indicate that the  ⫺AR1 is present in 39.7% of trigeminal neurons, and importantly, exhibits a 65.2% co-expression with TRPV1, a marker for a major subset of trigeminal nociceptors. Pretreatment with denopamine, a  ⫺AR1 agonist, had no effect on bradykinin-evoked release of iCGRP or [Ca]i levels under basal conditions. However, previous studies have demonstrated that BK primes GPCR signaling in trigeminal neurons (Patwardhan et al., J Neuroscience 2005). Therefore, we pre-treated cultures with BK (10 uM) and observed the development of a rapid (⬍10min), significant (p⬍0.01) and concentration-dependent denopamine inhibition of both BK-evoked CGRP release and changes in [Ca]i. Collectively, these preliminary studies are consistent with the hypothesis that activation of the  adrenergic receptor inhibits trigeminal nociceptors under prior conditions that involve release of the inflammatory mediator bradykinin. This work further suggests the prospect of utilizing the  adrenergics in the treatment of pain. Supported in part by F30 DE017307.
(674) Seeing the world through the lens of pain: Does chronic lower body pain compress visual perception of distance? J Augustyn, A Cook, P Brawer; The Miriam Hospital/Brown Medical School, Providence, RI Chronic pain has profound effects across a broad spectrum of biopsychosocial variables, including affective state, motor function, sleep, and the maintenance of meaningful social relationships. It commonly affects individuals’ interactions with their physical environments through psychological variables such as pain-related fear, disability perception, and avoidance behaviors. This pilot study examined whether chronic pain also influences a more fundamental neurocognitive process: the visual perception of distance. We compared distance perception in 49 patients (63.3% female; mean age 46.63 yrs, SD ⫽ 10.27) undergoing evaluation for treatment at a multidisciplinary pain management clinic and 49 healthy controls (65.3% female; mean age 41.13 yrs, SD ⫽ 11.13). All patients reported low back and/or lower extremity pain as their primary pain condition. Average duration of chronic pain was 7.71 years (SD ⫽ 7.38). Both patients and controls were asked to estimate the distance from their point of view to a target placed 13.4 meters (44 feet) away in a hallway. Patients underestimated distance (M ⫽ 10.63 m, SD ⫽ 3.83) relative to controls (M ⫽ 12.06 m, SD ⫽ 4.06); this difference approached significance (p ⫽ .07). Distance estimates were weakly correlated with self-report ratings of pain duration (r ⫽ .22), positive affect (r ⫽ .17), CRPP pain beliefs (r ⫽ ⫺.25), and TSK fear of movement scores (r ⫽ .18). These preliminary findings are consistent with an emerging view in cognitive science that visual perception is informed by the physical state of the body and suggest that pain sufferers may literally see the world differently than non-sufferers do. Effects of chronic pain on visual perception have theoretical significance for understanding how pain impacts functionality (e.g., walking, driving). Such effects may also have clinical significance as measures of pain impact and therapeutic progression and as potential targets for neurocognitive remediation interventions.