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Co-occurrence of posttraumatic stress symptoms, pain, and disability 12 months after traumatic injury

imageAbstractIntroduction:Chronic pain is common after traumatic injury and frequently co-occurs with posttraumatic stress disorder (PTSD) and PTSD symptoms (PTSS).Objectives:This study sought to understand the association between probable PTSD, PTSS, and pain.Methods:Four hundred thirty-three participants were recruited from the Victorian Orthopaedic Trauma Outcomes Registry and Victorian State Trauma Registry and completed outcome measures. Participants were predominantly male (n = 324, 74.8%) and aged 17-75 years at the time of their injury (M = 44.83 years, SD = 14.16). Participants completed the Posttraumatic Stress Disorder Checklist, Brief Pain Inventory, Pain Catastrophizing Scale, Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia, EQ-5D-3L and Roland-Morris Disability Questionnaire 12 months after hospitalization for traumatic injury. Data were linked with injury and hospital admission data from the trauma registries.Results:Those who reported having current problems with pain were 3 times more likely to have probable PTSD than those without pain. Canonical correlation showed that pain outcomes (pain severity, interference, catastrophizing, kinesiophobia, self-efficacy, and disability) were associated with all PTSSs, but especially symptoms of cognition and affect, hyperarousal, and avoidance. Posttraumatic stress disorder symptoms, on the contrary, were predominantly associated with high catastrophizing and low self-efficacy. When controlling for demographics, pain and injury severity, depression, and self-efficacy explained the greatest proportion of the total relationship between PTSS and pain-related disability.Conclusion:Persons with both PTSS and chronic pain after injury may need tailored interventions to overcome fear-related beliefs and to increase their perception that they can engage in everyday activities, despite their pain.
Introduction:
Chronic pain is common after traumatic injury and frequently co-occurs with posttraumatic stress disorder (PTSD) and PTSD symptoms (PTSS).
Objectives:
This study sought to understand the association between probable PTSD, PTSS, and pain.
Methods:
Four hundred thirty-three participants were recruited from the Victorian Orthopaedic Trauma Outcomes Registry and Victorian State Trauma Registry and completed outcome measures. Participants were predominantly male (n = 324, 74.8%) and aged 17-75 years at the time of their injury (M = 44.83 years, SD = 14.16). Participants completed the Posttraumatic Stress Disorder Checklist, Brief Pain Inventory, Pain Catastrophizing Scale, Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia, EQ-5D-3L and Roland-Morris Disability Questionnaire 12 months after hospitalization for traumatic injury. Data were linked with injury and hospital admission data from the trauma registries.
Results:
Those who reported having current problems with pain were 3 times more likely to have probable PTSD than those without pain. Canonical correlation showed that pain outcomes (pain severity, interference, catastrophizing, kinesiophobia, self-efficacy, and disability) were associated with all PTSSs, but especially symptoms of cognition and affect, hyperarousal, and avoidance. Posttraumatic stress disorder symptoms, on the contrary, were predominantly associated with high catastrophizing and low self-efficacy. When controlling for demographics, pain and injury severity, depression, and self-efficacy explained the greatest proportion of the total relationship between PTSS and pain-related disability.
Conclusion:
Persons with both PTSS and chronic pain after injury may need tailored interventions to overcome fear-related beliefs and to increase their perception that they can engage in everyday activities, despite their pain.

Co-occurrence of posttraumatic stress symptoms, pain, and disability 12 months after traumatic injury


Orginally Published At: PAIN Reports

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Pharmacoeconomics of genotyping-based treatment decisions in patients with chronic pain

imageAbstractIntroduction:Genotyping-based treatment decisions may optimize treatment response and minimize adverse drug events (ADEs) in patients with chronic pain.Objectives:To estimate the financial impact of genotyping-based treatment decisions in patients with moderate to severe chronic pain in a managed care setting.Methods:A budget impact model was built with a 1-year time horizon to estimate costs of genotyping-based treatment decisions in a 1000-patient cohort. The model includes drug costs, type and cost of ADEs, distribution of treatments used, and genotyping costs. Event rates and health care costs were derived from primary literature. Three patient cohorts were assessed with and without genotyping-based treatment decisions: no genetic testing; 50% genetic testing; and 100% genetic testing. Sensitivity analysis was performed varying costs, adherence, and the percentage of patients treated according to genotyping results.Results:Medical and ADE costs varied by patient severity and genotyping rates. Without genotyping, drug and ADE costs ranged from $1,544,377 to $24,313,844. With genotyping-based treatment, total costs ranged from $1,780,922 to $18,868,032. Sensitivity analysis, varying costs, adherence, and genotyping rates suggested genotyping improves outcomes and is cost saving in patients with chronic pain.Conclusion:Genotyping-based treatment costs are offset by reduced medication utilization and adverse event costs. Genotyping should be considered for patients with chronic pain in clinical practice and within clinical trials.
Introduction:
Genotyping-based treatment decisions may optimize treatment response and minimize adverse drug events (ADEs) in patients with chronic pain.
Objectives:
To estimate the financial impact of genotyping-based treatment decisions in patients with moderate to severe chronic pain in a managed care setting.
Methods:
A budget impact model was built with a 1-year time horizon to estimate costs of genotyping-based treatment decisions in a 1000-patient cohort. The model includes drug costs, type and cost of ADEs, distribution of treatments used, and genotyping costs. Event rates and health care costs were derived from primary literature. Three patient cohorts were assessed with and without genotyping-based treatment decisions: no genetic testing; 50% genetic testing; and 100% genetic testing. Sensitivity analysis was performed varying costs, adherence, and the percentage of patients treated according to genotyping results.
Results:
Medical and ADE costs varied by patient severity and genotyping rates. Without genotyping, drug and ADE costs ranged from $1,544,377 to $24,313,844. With genotyping-based treatment, total costs ranged from $1,780,922 to $18,868,032. Sensitivity analysis, varying costs, adherence, and genotyping rates suggested genotyping improves outcomes and is cost saving in patients with chronic pain.
Conclusion:
Genotyping-based treatment costs are offset by reduced medication utilization and adverse event costs. Genotyping should be considered for patients with chronic pain in clinical practice and within clinical trials.

Pharmacoeconomics of genotyping-based treatment decisions in patients with chronic pain


Orginally Published At: PAIN Reports

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Regular physical activity prevents development of chronic muscle pain through modulation of supraspinal opioid and serotonergic mechanisms

imageAbstractIntroduction:It is generally believed that exercise produces its effects by activating central opioid receptors; there are little data that support this claim. The periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) are key nuclei in opioid-induced analgesia, and opioids interact with serotonin to produce analgesia.Objectives:The purpose was to examine central inhibitory mechanisms involved in analgesia produced by wheel running.Methods:C57/Black6 mice were given access to running wheels in their home cages before induction of chronic muscle hyperalgesia and compared with those without running wheels. Systemic, intra-PAG, and intra-RVM naloxone tested the role of central opioid receptors in the antinociceptive effects of wheel running in animals with muscle insult. Immunohistochemistry for the serotonin transporter (SERT) in the spinal cord and RVM, and pharmacological blockade of SERT, tested whether the serotonin system was modulated by muscle insult and wheel running.Results:Wheel running prevented the development of muscle hyperalgesia. Systemic naloxone, intra-PAG naloxone, and intra-RVM naloxone reversed the antinociceptive effect of wheel running in animals that had received muscle insult. Induction of chronic muscle hyperalgesia increased SERT in the RVM, and blockade of SERT reversed the hyperalgesia in sedentary animals. Wheel running reduced SERT expression in animals with muscle insult. The serotonin transporter in the superficial dorsal horn of the spinal cord was unchanged after muscle insult, but increased after wheel running.Conclusion:These data support the hypothesis that wheel running produced analgesia through central inhibitory mechanisms involving opioidergic and serotonergic systems.
Introduction:
It is generally believed that exercise produces its effects by activating central opioid receptors; there are little data that support this claim. The periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) are key nuclei in opioid-induced analgesia, and opioids interact with serotonin to produce analgesia.
Objectives:
The purpose was to examine central inhibitory mechanisms involved in analgesia produced by wheel running.
Methods:
C57/Black6 mice were given access to running wheels in their home cages before induction of chronic muscle hyperalgesia and compared with those without running wheels. Systemic, intra-PAG, and intra-RVM naloxone tested the role of central opioid receptors in the antinociceptive effects of wheel running in animals with muscle insult. Immunohistochemistry for the serotonin transporter (SERT) in the spinal cord and RVM, and pharmacological blockade of SERT, tested whether the serotonin system was modulated by muscle insult and wheel running.
Results:
Wheel running prevented the development of muscle hyperalgesia. Systemic naloxone, intra-PAG naloxone, and intra-RVM naloxone reversed the antinociceptive effect of wheel running in animals that had received muscle insult. Induction of chronic muscle hyperalgesia increased SERT in the RVM, and blockade of SERT reversed the hyperalgesia in sedentary animals. Wheel running reduced SERT expression in animals with muscle insult. The serotonin transporter in the superficial dorsal horn of the spinal cord was unchanged after muscle insult, but increased after wheel running.
Conclusion:
These data support the hypothesis that wheel running produced analgesia through central inhibitory mechanisms involving opioidergic and serotonergic systems.

Regular physical activity prevents development of chronic muscle pain through modulation of supraspinal opioid and serotonergic mechanisms


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Effect of bupivacaine lozenges on oral mucositis pain: a randomized controlled multicenter phase II study

imageAbstractIntroduction:A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management.Objective:The primary end point was the difference between the intervention group (Lozenge group) and the Control group in daily mean pain scores in the oral cavity or pharynx (whichever was higher).Method:Fifty patients from 2 hospitals in Denmark were randomized 1:1 to 7 days of treatment with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing data.Results:Mean pain in the oral cavity or pharynx (whichever was higher) was significantly lower 60 minutes after taking lozenges (35 mm [n = 22]) than for the Control group (51 mm [n = 16]) (difference between groups −16 mm, 95% confidence interval: −26 to −6, P = 0.0032). Pain in the oral cavity was also significantly lower in the Lozenge group (18 mm) vs the Control group (36 mm, P = 0.0002). Pharyngeal mucositis pain did not differ significantly (37 mm [Lozenge group] vs 48 mm [Control group], P = 0.0630). No serious adverse events were reported.Conclusion:These results show that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis.ClinicalTrials.gov:NCT02252926.
Introduction:
A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management.
Objective:
The primary end point was the difference between the intervention group (Lozenge group) and the Control group in daily mean pain scores in the oral cavity or pharynx (whichever was higher).
Method:
Fifty patients from 2 hospitals in Denmark were randomized 1:1 to 7 days of treatment with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing data.
Results:
Mean pain in the oral cavity or pharynx (whichever was higher) was significantly lower 60 minutes after taking lozenges (35 mm [n = 22]) than for the Control group (51 mm [n = 16]) (difference between groups −16 mm, 95% confidence interval: −26 to −6, P = 0.0032). Pain in the oral cavity was also significantly lower in the Lozenge group (18 mm) vs the Control group (36 mm, P = 0.0002). Pharyngeal mucositis pain did not differ significantly (37 mm [Lozenge group] vs 48 mm [Control group], P = 0.0630). No serious adverse events were reported.
Conclusion:
These results show that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis.
ClinicalTrials.gov:
NCT02252926.

Effect of bupivacaine lozenges on oral mucositis pain: a randomized controlled multicenter phase II study


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Pediatric chronic pain programs: current and ideal practice

imageAbstractIntroduction:The treatment of youth with chronic pain has improved in recent years. However, because pediatric chronic pain programs are not governed by international standards, the development and implementation of new initiatives may be limited.Objectives:The objectives of this study were to identify the features of programs as they exist at present and to determine what features they should have in an ideal state.Methods:A web-based international survey was used to collect information. The survey contained 86 questions seeking respondent professional demographic data and information about the pain program with which the respondent was affiliated at the time (program organization, types of pain problem treated, professionals involved, services provided, size of the program, research, professional training, public education and advocacy, and funding sources).Results:Respondents were 136 pediatric pain experts representing different specialties located in 12 countries. Most respondents indicated that ideal programs would have a multidisciplinary staff; provide a wide range of treatments for different chronic pain problems; integrate research, formal clinical training of specialists, and public education and advocacy into their activities; and be an accredited part of the public health system.Conclusions:The results of this survey may be useful for health care professionals interested in treating chronic pain in children and adolescents and for policy makers concerned with improving the care given to these children and their families.
Introduction:
The treatment of youth with chronic pain has improved in recent years. However, because pediatric chronic pain programs are not governed by international standards, the development and implementation of new initiatives may be limited.
Objectives:
The objectives of this study were to identify the features of programs as they exist at present and to determine what features they should have in an ideal state.
Methods:
A web-based international survey was used to collect information. The survey contained 86 questions seeking respondent professional demographic data and information about the pain program with which the respondent was affiliated at the time (program organization, types of pain problem treated, professionals involved, services provided, size of the program, research, professional training, public education and advocacy, and funding sources).
Results:
Respondents were 136 pediatric pain experts representing different specialties located in 12 countries. Most respondents indicated that ideal programs would have a multidisciplinary staff; provide a wide range of treatments for different chronic pain problems; integrate research, formal clinical training of specialists, and public education and advocacy into their activities; and be an accredited part of the public health system.
Conclusions:
The results of this survey may be useful for health care professionals interested in treating chronic pain in children and adolescents and for policy makers concerned with improving the care given to these children and their families.

Pediatric chronic pain programs: current and ideal practice


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Differences in opioid prescribing in low back pain patients with and without depression: a cross-sectional study of a national sample from the United States

imageAbstractIntroduction:Low back pain (LBP) is among the leading indications for the prescription of opioid analgesics in clinical practice. There is increasing evidence suggesting that these agents may have diminished efficacy in the treatment of LBP.Objectives:We evaluated the relationship between depression, the probability of receiving an opioid prescription, and the amount of morphine equivalent amounts prescribed per year among patients with LBP using nationwide data.Methods:A cross-sectional analysis was performed on existing data from the Medical Expenditure Panel Survey data set from the period 2004 to 2009. Demographic, medical condition, Patient Health Questionnaire-2 responses, and prescription drug information were obtained on 56,811,864 weighted person-years of data from individuals aged 18 to 65 with an ICD-9 code specific to LBP.Results:Increases in PHQ-2 score, as well a positive screen for depression, were associated with an increased probability of being prescribed opioid therapy and more morphine equivalents per year.Conclusion:Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy.
Introduction:
Low back pain (LBP) is among the leading indications for the prescription of opioid analgesics in clinical practice. There is increasing evidence suggesting that these agents may have diminished efficacy in the treatment of LBP.
Objectives:
We evaluated the relationship between depression, the probability of receiving an opioid prescription, and the amount of morphine equivalent amounts prescribed per year among patients with LBP using nationwide data.
Methods:
A cross-sectional analysis was performed on existing data from the Medical Expenditure Panel Survey data set from the period 2004 to 2009. Demographic, medical condition, Patient Health Questionnaire-2 responses, and prescription drug information were obtained on 56,811,864 weighted person-years of data from individuals aged 18 to 65 with an ICD-9 code specific to LBP.
Results:
Increases in PHQ-2 score, as well a positive screen for depression, were associated with an increased probability of being prescribed opioid therapy and more morphine equivalents per year.
Conclusion:
Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy.

Differences in opioid prescribing in low back pain patients with and without depression: a cross-sectional study of a national sample from the United States


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Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study

imageAbstractIntroduction:Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models.Objectives:In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL).Methods:In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain.Results:Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy.Conclusion:Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.
Introduction:
Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models.
Objectives:
In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL).
Methods:
In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain.
Results:
Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy.
Conclusion:
Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study


Orginally Published At: PAIN Reports