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213 NEURONAL PENTRAXIN 1 CONTRIBUTES TO THE DESCENDING MODULATION OF NEUROPATHIC PAIN
Poster Sessions / European Journal of Pain 13 (2009) S55–S285
Methods: We performed a randomized controlled study in 12 healthy volunteers aged 21–54 (Md = 25.5) yrs. and paralleled with respect to gender. The study protocol comprised the assessment of dynamic mechanical and thermal pain sensitivity (perceptual wind-up) before and after an IWP (15 N) or hot water immersion trial (HIT; 47.5º C) of 2 min duration. Wind-up was induced either by 10 repetitive (1 Hz) contact heat (49ºC) or ballistic impact stimuli (9 m/s) on the phalanges of the non-dominant hand. Cardiovascular and respiratory activity as well as pain experience were continuously monitored (Biopac Systems, Inc.). Results: The HIT but not the IWP reliably produced a significant mean blood pressure increase of 5% (p = .04). While prominent reductions of ratings for heterotopically applied mechanical and thermal noxious stimuli could be observed during the HIT, this was only the case for thermal test stimuli in the IWP condition. Conclusions: The IWP proved to be a valid paradigm for DNIC induction, unconfounded by BRS-related hypoalgesia. The data also indicate a modality specificity of DNIC in man. The study was supported by grants from the Luxembourg University and the Ministry of Research (AFR TR-PHD BFR07–102). 211 PRELIMINARY EXPERIMENTAL DATA REGARDING THE EFFECTS OF TWO 5HT1 RECEPTOR AGONISTS IN NOCICEPTION L. Tartau *. Gr.T. Popa University of Medicine and Pharmacy, Iasi, Romania Abstract: Serotonin is a major component of the inflammatory chemical milieu and contributes to the pain of tissue injury via an action on multiple receptor subtypes. Buspirone, is a partial 5-HT1 A receptor agonist buspirone which is widely used for treating anxiety. Sumatriptan is a 5HT 1B/1D serotonin receptor agonist use used to treat severe migraine headaches. The aim of the present study was to establish the effects of two 5HT1 serotonine receptor subtype agonists in cutaneous and visceral pain models in mice. Material and method: The experiment was carried out, with white male mice (20–25 g), distributed into 3 groups of 7 animals each, treated intraperitoneally as follows: Group I: saline solution 0.3 ml (Control); Group II (BUS): buspirone 8 mg/kbw; Group III (SUM): sumatriptan 30 mg/kbw. The nociceptive cutaneous testing was performed using hot plate assay. The model of visceral pain consists of inflammatory cystitis after intraperitoneal injection of cyclophosphamide (200 mg/kbw). Data were statistically analyzed using SPSS program. Results: Buspirone significantly increased the response latency in the mouse hot plate test and markedly decreased the nociceptive behavioral manifestations in experimental chemical cystitis model. Sumatriptan increased pain threshold in the model of thermal noxious stimulation, but do not influence painful behavioral manifestations in the visceral pain test. Conclusions: Using the mouse model of acute pain hot plate analgesia meter, we found antinociceptive properties of both buspirone and sumatriptan. Buspirone is antinociceptor, while sumatriptan possesses no analgesic properties, in visceral pain model. 212 BOTH VISCERAL AND SOMATIC ENDOGENOUS PAIN MODULATION ARE ABNORMAL IN IRRITABLE BOWEL SYNDROME (IBS) PATIENTS: A META-ANALYSIS ACROSS DIFFERENT RACES C. Wilder-Smith1,2 *. 1 Brain-Gut Research Group, Bern, Switzerland; 2 Dept Medicine, National University Singapore, Singapore, Singapore Recent psychophysical and brain fMRI studies have shown abnormal endogenous visceral or somatic pain modulation in smaller numbers of IBS patients of different races. In this meta-analysis visceral and somatic pain modulation, specifically diffuse noxious inhibitory controls (DNIC), were compared across different races in a large number of IBS and healthy subjects. DNIC was examined
S69
by heterotopic stimulation using rectal distension (visceral DNIC) or electrical hand stimulation (somatic DNIC) applied alone and together with cold foot stimulation as the conditioning stimulation. DNIC is the change in primary pain during simultaneous application of the conditioning pain. Stimulation intensities were between 50–70 on 0–100 VAS. Mean somatic and visceral DNIC (95%CI) were similar in the 84 IBS patients (decrease in primary pain intensity −0.5 (−5.4–4.4) and −2.6 (−5.9–1.0), resp.) and in the 69 matched healthy controls (−13.4 (−18–−9) and −8.6 (−15–−3), resp., but different between IBS and controls (p < 0.0001). The pooled change in visceral and somatic pain due to DNIC was −6% (−13–1) in IBS and −22% (−28– −17) in controls (p < 0.0001). 54% of IBS patients versus 9% of controls showed pain facilitation instead of the expected inhibition (p < 0.0001). The magnitude of DNIC was influenced by race (white > asian > black, p < 0.001). Both visceral and somatic pain modulation were highly abnormal across all races in this large group of IBS patients, implying a generalised dysfunction of sensory modulation. There are significant racial differences in endogenous pain modulation. Facilitation during heterotopic stimulation is infrequent in controls and is therefore quite specific for IBS. 213 NEURONAL PENTRAXIN 1 CONTRIBUTES TO THE DESCENDING MODULATION OF NEUROPATHIC PAIN A. Zapata1 *, R. Schepers1 , B. Gehrke1 , E. Oh1 , R. Trullas2 , T. Shippenberg1 . 1 National Institute on Drug Abuse, Baltimore, United States; 2 Institut d’Investigacions Biomediques de Barcelona, CSIC/IDIBAPS, Barcelona, Spain Background and Aims: The neuronal pentraxin family of proteins promotes synaptic clustering of AMPA glutamate receptors and synaptic plasticity. Increased glutamatergic signaling in the rostral ventromedial medulla (RVM), a brainstem region important for the descending modulation of nociception, is implicated in the maintenance of neuropathic pain. We have investigated the involvement of neuronal pentraxin 1 (NP1) in a neuropathic pain model in rodents. Methods: We have used gene knock-out techniques and viralmediated silencing/over-expression of NP1 in the RVM in vivo to address the involvement of this protein in the spared nerve injury (SNI) model of neuropathic pain in rodents. Mechanical allodynia (Von Frey filaments) and hyperalgesia (pin prick test) was evaluated in the sural nerve territory of both paws. Results: Mechanical allodynia associated with SNI is reduced in NP1 knock-out mice. Consistent with the role of the RVM in descending facilitation of nerve injury-evoked pain, rescuing NP1 expression therein abolishes the phenotype of knock-out mice. Silencing NP1 in the RVM of rats prior to nerve injury prevents the development of allodynia and hyperalgesia. Furthermore, when silencing occurs after SNI, the expression of allodynia and hyperalgesia is reversed. Modulation of NP1 expression did not change basal nociception in the ipsilateral paw nor alter mechanical thresholds in the contralateral paw after injury. Conclusions: These data demonstrate a specific role of NP1 in the pathogenesis of neuropathic pain and suggest that targeting this protein may provide a novel treatment for persistent pain arising from diverse etiologies. 214 THE EFFECT OF PERSONALITY ON CENTRAL PAIN PROCESSING C. Berna1,2 *, A. Reinecke1 , E.A. Holmes1 , G.M. Goodwin1 , I. Tracey2 . 1 Department of Psychiatry, University of Oxford, Oxford, United Kingdom; 2 Centre for Functional Magnetic Imaging of the Brain (FMRIB), Departments of Clinical Neurology and Anaesthetics, University of Oxford, Oxford, United Kingdom Background and Aims: Neuroticism is a personality trait, predisposing to depression and associated with negative outcomes
Methods: We performed a randomized controlled study in 12 healthy volunteers aged 21–54 (Md = 25.5) yrs. and paralleled with respect to gender. The study protocol comprised the assessment of dynamic mechanical and thermal pain sensitivity (perceptual wind-up) before and after an IWP (15 N) or hot water immersion trial (HIT; 47.5º C) of 2 min duration. Wind-up was induced either by 10 repetitive (1 Hz) contact heat (49ºC) or ballistic impact stimuli (9 m/s) on the phalanges of the non-dominant hand. Cardiovascular and respiratory activity as well as pain experience were continuously monitored (Biopac Systems, Inc.). Results: The HIT but not the IWP reliably produced a significant mean blood pressure increase of 5% (p = .04). While prominent reductions of ratings for heterotopically applied mechanical and thermal noxious stimuli could be observed during the HIT, this was only the case for thermal test stimuli in the IWP condition. Conclusions: The IWP proved to be a valid paradigm for DNIC induction, unconfounded by BRS-related hypoalgesia. The data also indicate a modality specificity of DNIC in man. The study was supported by grants from the Luxembourg University and the Ministry of Research (AFR TR-PHD BFR07–102). 211 PRELIMINARY EXPERIMENTAL DATA REGARDING THE EFFECTS OF TWO 5HT1 RECEPTOR AGONISTS IN NOCICEPTION L. Tartau *. Gr.T. Popa University of Medicine and Pharmacy, Iasi, Romania Abstract: Serotonin is a major component of the inflammatory chemical milieu and contributes to the pain of tissue injury via an action on multiple receptor subtypes. Buspirone, is a partial 5-HT1 A receptor agonist buspirone which is widely used for treating anxiety. Sumatriptan is a 5HT 1B/1D serotonin receptor agonist use used to treat severe migraine headaches. The aim of the present study was to establish the effects of two 5HT1 serotonine receptor subtype agonists in cutaneous and visceral pain models in mice. Material and method: The experiment was carried out, with white male mice (20–25 g), distributed into 3 groups of 7 animals each, treated intraperitoneally as follows: Group I: saline solution 0.3 ml (Control); Group II (BUS): buspirone 8 mg/kbw; Group III (SUM): sumatriptan 30 mg/kbw. The nociceptive cutaneous testing was performed using hot plate assay. The model of visceral pain consists of inflammatory cystitis after intraperitoneal injection of cyclophosphamide (200 mg/kbw). Data were statistically analyzed using SPSS program. Results: Buspirone significantly increased the response latency in the mouse hot plate test and markedly decreased the nociceptive behavioral manifestations in experimental chemical cystitis model. Sumatriptan increased pain threshold in the model of thermal noxious stimulation, but do not influence painful behavioral manifestations in the visceral pain test. Conclusions: Using the mouse model of acute pain hot plate analgesia meter, we found antinociceptive properties of both buspirone and sumatriptan. Buspirone is antinociceptor, while sumatriptan possesses no analgesic properties, in visceral pain model. 212 BOTH VISCERAL AND SOMATIC ENDOGENOUS PAIN MODULATION ARE ABNORMAL IN IRRITABLE BOWEL SYNDROME (IBS) PATIENTS: A META-ANALYSIS ACROSS DIFFERENT RACES C. Wilder-Smith1,2 *. 1 Brain-Gut Research Group, Bern, Switzerland; 2 Dept Medicine, National University Singapore, Singapore, Singapore Recent psychophysical and brain fMRI studies have shown abnormal endogenous visceral or somatic pain modulation in smaller numbers of IBS patients of different races. In this meta-analysis visceral and somatic pain modulation, specifically diffuse noxious inhibitory controls (DNIC), were compared across different races in a large number of IBS and healthy subjects. DNIC was examined
S69
by heterotopic stimulation using rectal distension (visceral DNIC) or electrical hand stimulation (somatic DNIC) applied alone and together with cold foot stimulation as the conditioning stimulation. DNIC is the change in primary pain during simultaneous application of the conditioning pain. Stimulation intensities were between 50–70 on 0–100 VAS. Mean somatic and visceral DNIC (95%CI) were similar in the 84 IBS patients (decrease in primary pain intensity −0.5 (−5.4–4.4) and −2.6 (−5.9–1.0), resp.) and in the 69 matched healthy controls (−13.4 (−18–−9) and −8.6 (−15–−3), resp., but different between IBS and controls (p < 0.0001). The pooled change in visceral and somatic pain due to DNIC was −6% (−13–1) in IBS and −22% (−28– −17) in controls (p < 0.0001). 54% of IBS patients versus 9% of controls showed pain facilitation instead of the expected inhibition (p < 0.0001). The magnitude of DNIC was influenced by race (white > asian > black, p < 0.001). Both visceral and somatic pain modulation were highly abnormal across all races in this large group of IBS patients, implying a generalised dysfunction of sensory modulation. There are significant racial differences in endogenous pain modulation. Facilitation during heterotopic stimulation is infrequent in controls and is therefore quite specific for IBS. 213 NEURONAL PENTRAXIN 1 CONTRIBUTES TO THE DESCENDING MODULATION OF NEUROPATHIC PAIN A. Zapata1 *, R. Schepers1 , B. Gehrke1 , E. Oh1 , R. Trullas2 , T. Shippenberg1 . 1 National Institute on Drug Abuse, Baltimore, United States; 2 Institut d’Investigacions Biomediques de Barcelona, CSIC/IDIBAPS, Barcelona, Spain Background and Aims: The neuronal pentraxin family of proteins promotes synaptic clustering of AMPA glutamate receptors and synaptic plasticity. Increased glutamatergic signaling in the rostral ventromedial medulla (RVM), a brainstem region important for the descending modulation of nociception, is implicated in the maintenance of neuropathic pain. We have investigated the involvement of neuronal pentraxin 1 (NP1) in a neuropathic pain model in rodents. Methods: We have used gene knock-out techniques and viralmediated silencing/over-expression of NP1 in the RVM in vivo to address the involvement of this protein in the spared nerve injury (SNI) model of neuropathic pain in rodents. Mechanical allodynia (Von Frey filaments) and hyperalgesia (pin prick test) was evaluated in the sural nerve territory of both paws. Results: Mechanical allodynia associated with SNI is reduced in NP1 knock-out mice. Consistent with the role of the RVM in descending facilitation of nerve injury-evoked pain, rescuing NP1 expression therein abolishes the phenotype of knock-out mice. Silencing NP1 in the RVM of rats prior to nerve injury prevents the development of allodynia and hyperalgesia. Furthermore, when silencing occurs after SNI, the expression of allodynia and hyperalgesia is reversed. Modulation of NP1 expression did not change basal nociception in the ipsilateral paw nor alter mechanical thresholds in the contralateral paw after injury. Conclusions: These data demonstrate a specific role of NP1 in the pathogenesis of neuropathic pain and suggest that targeting this protein may provide a novel treatment for persistent pain arising from diverse etiologies. 214 THE EFFECT OF PERSONALITY ON CENTRAL PAIN PROCESSING C. Berna1,2 *, A. Reinecke1 , E.A. Holmes1 , G.M. Goodwin1 , I. Tracey2 . 1 Department of Psychiatry, University of Oxford, Oxford, United Kingdom; 2 Centre for Functional Magnetic Imaging of the Brain (FMRIB), Departments of Clinical Neurology and Anaesthetics, University of Oxford, Oxford, United Kingdom Background and Aims: Neuroticism is a personality trait, predisposing to depression and associated with negative outcomes