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(148) Antinociceptive effects of lumbar intrathecal neuropeptide y-saporin
Abstracts (148) Antinociceptive effects of lumbar intrathecal neuropeptide y-saporin R Kline, L Lemons, R Wiley; VA Tennessee Valley Healthcare System, Nashville, TN Society for Neuroscience abstract
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Trigeminal Pain Mechanisms (150) Supraspinal modulation of trigeminal nociception and pain: Emotional controls (ECON) and diffuse noxious inhibitory controls (DNIC) J Rhudy, A Williams; The University of Tulsa, Tulsa, OK The purpose of this study was to examine the modulation of trigeminal pain and nociception by two forms of supraspinal influences: emotional controls of nociception (ECON) and diffuse noxious inhibitory controls (DNIC). Trigeminal nociception and pain was assessed from the nociceptive blink reflex and pain ratings, respectively, following noxious stimulations delivered by a custom concentric electrode designed to selectively activate nociceptive fibers. ECON were engaged by the presentation of standardized picture stimuli (pleasant, neutral, and unpleasant) that have been shown to reliably evoke pleasure-induced inhibition and displeasure-induced facilitation of pain and spinal nociception. DNIC were engaged by the application of a forearm ischemia pain task. Results suggested ECON and DNIC modulated trigeminal nociception and pain. Emotional valence/pleasure (as assessed from trend analysis) explained 51% of the variance in pain ratings and 20% of the variance in blinks. Pain and nociceptive blinks were facilitated by unpleasant pictures and inhibited by pleasant pictures. Additionally, the DNIC task (forearm ischemia) inhibited pain and the blink reflex. The baseline vs. ischemia comparison for DNIC explained 17% of the variance in pain report and 7% of the variance in blinks. Exploratory analyses suggested ECON and DNIC modulation were uncorrelated, providing preliminary evidence that they are independent processes. This paradigm has important implications for future research on the pathophysiology of head and face pain. All procedures used in this study were approved by The University of Tulsa IRB. This work was partially supported by a University of Tulsa Faculty Summer Development Fellowship awarded to Jamie L. Rhudy, Ph.D. and a University of Tulsa Student Research Grant from The University of Tulsa Office of Research awarded to Amy Williams, M.A.
(149) Reduced cold hyperalgesia, allodynia and anatomic effects of lumbar intrathecal NPY-saporin R Wiley, R Kline, IV, L Lemons; VA Tennessee Valley Healthcare System, Nashville, TN Lumbar intrathecal (i.t.) neuropeptide Y-saporin (NPY-sap) reduces dorsal horn NPY1R staining, produces hyporeflexia to nociceptive thermal and chemical stimulation and increases behaviors correlated with reduced nociception in thermal preference testing (TPT). In the present study, we sought to determine the following effects of lumbar i.t. NPYsap: 1 - baseline responsivity to a 15o/45oC thermal preference task (TPT), 2 - TPT after intra-plantar CFA, 3 - reflex behavior on cold plate at 0.3o and 10oC after CFA, 4 -dorsal horn staining of NPY peptide, mu opiate receptor (MOR), neurokinin-1 receptor (NK-1R), 5 - dorsal root ganglion (DRG) NPY receptor 1 (NPYR1) and Nissl staining. Long Evans female rats (18) were pre-trained on TPT until about 50% occupancy was reached for two adjacent compartments at 12oC and 45oC, then injected i.t. with NPY-sap (0ng, 500ng, 750ng). TPT was monitored for two months after which rats received bilateral hindpaw injection of CFA (100l s.c./paw) followed by cold plate and additional TPT testing. L4 DRG from three Sprague Dawley male rats injected with 1g NPY-sap were Nissl stained to identify poisoned neurons. After two weeks to one month, NPY-sap did not affect dorsal horn staining of NPY, MOR or NK-1R or DRG staining for NPY1R. Acute (48hr) NPY-sap possibly poisoned blank 0.43% of L4 DRG neurons, suggesting NPY-sap does not undergo significant retrograde transport. NPY-sap produced the following effects, 1- increased cold plate time in the TPT, 2 - decreased operant avoidance of cold after plantar CFA in the TPT, 3 - thermal hyporeflexia on a 0.3o and 10oC cold plate, 4 - a selective lesion of NPY1R expressing dorsal horn neurons. These results indicate a role for dorsal horn NPY1R in responses to noxious cold stimuli, possibly by modifying rostral transmission of nociceptive information.
Other (151) Pharmacological and non-pharmacological strategies for preventing analgesic tolerance to TENS J De Santana, K Sluka; University of Iowa, University of Iowa, IA Analgesia produced by low and high frequency TENS is mediated by release of - or ⌬-opioids, respectively. Repeated administration of low and high frequency TENS results in analgesic tolerance on the fourth day. Simultaneous administration of - and ⌬-opioid agonists or administration of cholecystokinin (CCK) receptor antagonists reduces tolerance to opioid agonists. Thus, we tested the hypotheses that 1) repeated administration of modulating frequency TENS, and 2) CCK receptor antagonists will prevent development of tolerance to TENS. The effects of repeated TENS on cutaneous and muscle hyperalgesia induced by knee joint inflammation (3% carrageenan/kaolin) were examined. In experiment 1, male Sprague-Dawley rats were randomly assigned to receive sham, mixed frequency, or alternating frequency TENS (n⫽6/group). Either mixed (4Hz and 100Hz administered at the same session) or alternating frequency (4Hz and 100Hz administered on alternating days) was administered daily (20 min) for 2 weeks to the inflamed knee joint. In experiment 2, rats were divided into groups: sham, high TENS, or low TENS treated systemically with either vehicle or proglumide (0.3, 1 and 3g) prior to TENS (n⫽6/group). Paw and joint withdrawal thresholds were assessed before and after application of TENS daily in both experiments. Repeated daily administration of either mixed or alternating frequency TENS delayed the onset of tolerance until the 10th day of treatment, i.e. TENS reduced hyperalgesia for the first 9 days of treatment. In the group treated with proglumide prior to TENS there was still a reversal of hyperalgesia by TENS on the fourth day when compared to a lack of effect of TENS in the vehicle treated group. These data suggest that repeated administration of modulating frequency TENS delays the onset of analgesic tolerance to TENS and systemic blockade of CCK receptors during application of TENS prevents tolerance to TENS.
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Trigeminal Pain Mechanisms (150) Supraspinal modulation of trigeminal nociception and pain: Emotional controls (ECON) and diffuse noxious inhibitory controls (DNIC) J Rhudy, A Williams; The University of Tulsa, Tulsa, OK The purpose of this study was to examine the modulation of trigeminal pain and nociception by two forms of supraspinal influences: emotional controls of nociception (ECON) and diffuse noxious inhibitory controls (DNIC). Trigeminal nociception and pain was assessed from the nociceptive blink reflex and pain ratings, respectively, following noxious stimulations delivered by a custom concentric electrode designed to selectively activate nociceptive fibers. ECON were engaged by the presentation of standardized picture stimuli (pleasant, neutral, and unpleasant) that have been shown to reliably evoke pleasure-induced inhibition and displeasure-induced facilitation of pain and spinal nociception. DNIC were engaged by the application of a forearm ischemia pain task. Results suggested ECON and DNIC modulated trigeminal nociception and pain. Emotional valence/pleasure (as assessed from trend analysis) explained 51% of the variance in pain ratings and 20% of the variance in blinks. Pain and nociceptive blinks were facilitated by unpleasant pictures and inhibited by pleasant pictures. Additionally, the DNIC task (forearm ischemia) inhibited pain and the blink reflex. The baseline vs. ischemia comparison for DNIC explained 17% of the variance in pain report and 7% of the variance in blinks. Exploratory analyses suggested ECON and DNIC modulation were uncorrelated, providing preliminary evidence that they are independent processes. This paradigm has important implications for future research on the pathophysiology of head and face pain. All procedures used in this study were approved by The University of Tulsa IRB. This work was partially supported by a University of Tulsa Faculty Summer Development Fellowship awarded to Jamie L. Rhudy, Ph.D. and a University of Tulsa Student Research Grant from The University of Tulsa Office of Research awarded to Amy Williams, M.A.
(149) Reduced cold hyperalgesia, allodynia and anatomic effects of lumbar intrathecal NPY-saporin R Wiley, R Kline, IV, L Lemons; VA Tennessee Valley Healthcare System, Nashville, TN Lumbar intrathecal (i.t.) neuropeptide Y-saporin (NPY-sap) reduces dorsal horn NPY1R staining, produces hyporeflexia to nociceptive thermal and chemical stimulation and increases behaviors correlated with reduced nociception in thermal preference testing (TPT). In the present study, we sought to determine the following effects of lumbar i.t. NPYsap: 1 - baseline responsivity to a 15o/45oC thermal preference task (TPT), 2 - TPT after intra-plantar CFA, 3 - reflex behavior on cold plate at 0.3o and 10oC after CFA, 4 -dorsal horn staining of NPY peptide, mu opiate receptor (MOR), neurokinin-1 receptor (NK-1R), 5 - dorsal root ganglion (DRG) NPY receptor 1 (NPYR1) and Nissl staining. Long Evans female rats (18) were pre-trained on TPT until about 50% occupancy was reached for two adjacent compartments at 12oC and 45oC, then injected i.t. with NPY-sap (0ng, 500ng, 750ng). TPT was monitored for two months after which rats received bilateral hindpaw injection of CFA (100l s.c./paw) followed by cold plate and additional TPT testing. L4 DRG from three Sprague Dawley male rats injected with 1g NPY-sap were Nissl stained to identify poisoned neurons. After two weeks to one month, NPY-sap did not affect dorsal horn staining of NPY, MOR or NK-1R or DRG staining for NPY1R. Acute (48hr) NPY-sap possibly poisoned blank 0.43% of L4 DRG neurons, suggesting NPY-sap does not undergo significant retrograde transport. NPY-sap produced the following effects, 1- increased cold plate time in the TPT, 2 - decreased operant avoidance of cold after plantar CFA in the TPT, 3 - thermal hyporeflexia on a 0.3o and 10oC cold plate, 4 - a selective lesion of NPY1R expressing dorsal horn neurons. These results indicate a role for dorsal horn NPY1R in responses to noxious cold stimuli, possibly by modifying rostral transmission of nociceptive information.
Other (151) Pharmacological and non-pharmacological strategies for preventing analgesic tolerance to TENS J De Santana, K Sluka; University of Iowa, University of Iowa, IA Analgesia produced by low and high frequency TENS is mediated by release of - or ⌬-opioids, respectively. Repeated administration of low and high frequency TENS results in analgesic tolerance on the fourth day. Simultaneous administration of - and ⌬-opioid agonists or administration of cholecystokinin (CCK) receptor antagonists reduces tolerance to opioid agonists. Thus, we tested the hypotheses that 1) repeated administration of modulating frequency TENS, and 2) CCK receptor antagonists will prevent development of tolerance to TENS. The effects of repeated TENS on cutaneous and muscle hyperalgesia induced by knee joint inflammation (3% carrageenan/kaolin) were examined. In experiment 1, male Sprague-Dawley rats were randomly assigned to receive sham, mixed frequency, or alternating frequency TENS (n⫽6/group). Either mixed (4Hz and 100Hz administered at the same session) or alternating frequency (4Hz and 100Hz administered on alternating days) was administered daily (20 min) for 2 weeks to the inflamed knee joint. In experiment 2, rats were divided into groups: sham, high TENS, or low TENS treated systemically with either vehicle or proglumide (0.3, 1 and 3g) prior to TENS (n⫽6/group). Paw and joint withdrawal thresholds were assessed before and after application of TENS daily in both experiments. Repeated daily administration of either mixed or alternating frequency TENS delayed the onset of tolerance until the 10th day of treatment, i.e. TENS reduced hyperalgesia for the first 9 days of treatment. In the group treated with proglumide prior to TENS there was still a reversal of hyperalgesia by TENS on the fourth day when compared to a lack of effect of TENS in the vehicle treated group. These data suggest that repeated administration of modulating frequency TENS delays the onset of analgesic tolerance to TENS and systemic blockade of CCK receptors during application of TENS prevents tolerance to TENS.