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Afghanistan-Era Veterans
Abstracts
Treatment Approaches (Medical/ Interventional) (273) Acute Postoperative Opioid Trajectories and Long-Term Outcomes in Pediatric Patients after Surgery M. Li and C. Ferland; Shriners Hospital for Children-Canada, Montreal The days following surgery encompass a critical period where the use of opioids predicts long-term outcomes in adults. It is currently unknown as to whether opioid consumption throughout the acute postoperative period is associated with long-term outcomes in pediatric patients. The aims of this study were to characterize opioid trajectories in the acute postoperative period, identify predictors of opioid trajectory membership and determine associations between opioid trajectories and long-term patient outcomes. Medication use, pain and mental health status were assessed at baseline in adolescents with idiopathic scoliosis who were schedule for spinal fusion surgery. Cumulative 6-hour opioid consumption was recorded for up to 5 days after spinal surgery. At 6 weeks and 6 months after surgery, medication use, pain and physical function were evaluated. Growth mixture modeling was used to identify opioid trajectories. The study included 106 patients. Mean cumulative opioid consumption in the acute postoperative period was 13.23 § 5.20 mg/kg. The model with the best fit contained 5 acute postoperative opioid trajectories and a quadratic term (AIC = 6703.26, BIC = 6767.19). Opioid trajectories differed in the total amount of opioids consumed and the rate of opioid intake over the acute postoperative period. Intraoperative epimorphine dose predicted the opioid trajectory membership (p = 0.0498). Opioid trajectory groups were significantly associated with pain at 6 weeks (p = 0.0103) and 6 months (p = 0.0457) after surgery. Intraoperative epimorphine dose predicts the opioid consumption in the acute postoperative period. Opioid consumption during this period is associated with long-term pain. Understanding the acute postoperative period and its association with baseline predictors and long-term patient outcomes will allow for personalized perioperative care.
(274) Novel Neurosteroid Intervention for Chronic Low Back Pain in Iraq/Afghanistan-Era Veterans J. Naylor, J. Kilts, R. Wagner, L. Shampine, G. Parke, S. Szabo, and C. Marx; Durham VA Medical Center, Durham, NC Chronic low back pain symptoms are extremely common among Iraq/Afghanistan-era Veterans. However, pharmacological management for pain is frequently suboptimal, and many Veterans experience persistent and unalleviated pain symptoms and/or intolerable side effects to pain medications. Current medications such as opioids that are frequently used to treat chronic pain symptoms have side effect risks such as respiratory depression, addiction, sedation, and potentially lethal interactions with other drugs. There is thus an acute and immediate need for the development of effective, safe, and non-habit-forming pharmacological treatments for chronic pain disorders. Neurosteroids are endogenous molecules that are enriched in human brain and hold promise for pain therapeutics. Data in rodent models demonstrate that neurosteroids exhibit pronounced analgesic actions, and our data in Iraq/Afghanistan-era Veterans suggest that neurosteroids are decreased in the setting of pain symptoms in clinical populations. Neurosteroids are hence logical candidates for pain alleviation and have not been tested yet for this indication. We thus conducted a 6-week randomized, double-blind, placebo-controlled trial of pregnenolone versus placebo to determine if adjunctive pregnenolone has therapeutic utility for the treatment of chronic low back pain in Iraq/Afghanistan-era Veterans. The primary outcome measure was average pain intensity ratings from a daily pain diary. Secondary outcomes included pain interference scores. Pregnenolone was extremely well-tolerated. Veterans randomized to pregnenolone reported significant reductions in low back pain relative to those randomized to placebo (pain diary p=0.024; pain recall p=0.010). Pain interference scores for “work” (p=0.040) and “activity” (p=0.031) were also improved in Veterans randomized to pregnenolone compared to placebo. Pregnenolone may thus represent a new intervention for pain conditions that is safe, well-tolerated, non-habit-forming, and potentially efficacious for the alleviation of pain symptoms in Iraq/Afghanistan-era Veterans.
The Journal of Pain
S43
(275) Somatosensory Predictors of Response to Pregabalin in Painful Chemotherapy-Induced Peripheral Neuropathy (CIPN): A Randomized, Placebo-Controlled, Crossover Study A. Hincker, K. Frey, L. Rao, N. Wagner-Johnston, A. Abdallah, B. Tan, M. Amin, T. Wildes, R. Shah, K. Bakos, P. Kalsson, and S. Haroutounian; Washington University, St. Louis, MO Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of a2d subunits of voltage-gated Ca2+ channels, such as pregabalin, have shown efficacy in reducing mechanical hypersensitivity in animal models of neuropathic pain. In addition, some data suggested that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased hypersensitivity to pinprick. We hypothesized that mechanical hypersensitivity, as quantified by decreased mechanical pain threshold (MPT) at the dorsal feet, would be predictive of a greater reduction in average daily pain in response to pregabalin versus placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600mg a day) and placebo in cross-over design. Twenty-three participants completed both arms and were eligible for efficacy analysis. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, p = 0.23) or worst pain (29.2% vs 16.0%, p = 0.13) from baseline. Post-hoc analysis of patients with CIPN caused by oxaliplatin only (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, p = 0.04). MPT was not significantly correlated with reduction in average pain (p = 0.20) or worst pain (p = 0.19) in response to pregabalin. In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN. This work was supported by the ASPIRE grant program by Pfizer, Inc.
(276) Acute Exercise Decreases Situational Pain Catastrophizing of a Noxious Stimulus R. Nevsimal, A. Awali, A. Alsouhibani, S. O’Melia, and M. Hoeger Bement; Marquette University, Milwaukee, WI There is limited evidence regarding the variability in pain response following exercise, including the impact of pain catastrophizing. The purpose of this study was to investigate the relation of the pain response after exercise with pain catastrophizing levels in young healthy individuals. Fifty-seven participants (20.75§1.81 years, 29 women) completed two randomized sessions (exercise and quiet rest). Exercise consisted of sustained submaximal isometric contraction of the knee extensors, performed until task failure. Temporal summation (TS) was assessed before and after exercise and quiet rest, by applying a constant mechanical stimulus to the index finger for one minute after reported pain threshold. During the one minute, participants were asked to rate their pain every 15 seconds (0-10 Numerical Pain Rating Scale). TS was calculated as the last pain rating minus the first pain rating. Pain catastrophizing scale (PCS) was completed at the beginning of the first session. Situational catastrophizing (S-PCS) was completed after each TS protocol. Based on the change in pain following exercise, participants were divided into two groups, responders (hypoalgesia) and nonresponders (no change or hyperalgesia). There was no difference in baseline PCS between groups (p=0.974). For S-PCS, there was a session x trial x group interaction (p<0.001). In the exercise session, responders had a reduction in S-PCS (p=0.001) while S-PCS increased in the non-responders (p=0.018). In the quiet rest session, S-PCS did not change (p=0.365). There was a significant correlation between the change in S-PCS and TS with exercise (r= 0.31, p=0.02) after controlling for the effect of baseline S-PCS and TS. Exercise impacts both central pain modulation and psychological attributes related to pain. This study provides further support for the integration of psychological and physiological aspects of nonpharmacological pain management with exercise interventions.
(277) Racial/Ethnic Disparities in Opioid Prescribing for LongBone Fractures at Emergency Department Discharge: A CrossSectional Analysis of 22 Centers from a Single Healthcare Delivery System R. Romanelli, Z. Shen, N. Szwerinski, A. Scott, and A. Pressman; Palo Alto Medical Foundation Research Institute, Palo Alto, CA
Treatment Approaches (Medical/ Interventional) (273) Acute Postoperative Opioid Trajectories and Long-Term Outcomes in Pediatric Patients after Surgery M. Li and C. Ferland; Shriners Hospital for Children-Canada, Montreal The days following surgery encompass a critical period where the use of opioids predicts long-term outcomes in adults. It is currently unknown as to whether opioid consumption throughout the acute postoperative period is associated with long-term outcomes in pediatric patients. The aims of this study were to characterize opioid trajectories in the acute postoperative period, identify predictors of opioid trajectory membership and determine associations between opioid trajectories and long-term patient outcomes. Medication use, pain and mental health status were assessed at baseline in adolescents with idiopathic scoliosis who were schedule for spinal fusion surgery. Cumulative 6-hour opioid consumption was recorded for up to 5 days after spinal surgery. At 6 weeks and 6 months after surgery, medication use, pain and physical function were evaluated. Growth mixture modeling was used to identify opioid trajectories. The study included 106 patients. Mean cumulative opioid consumption in the acute postoperative period was 13.23 § 5.20 mg/kg. The model with the best fit contained 5 acute postoperative opioid trajectories and a quadratic term (AIC = 6703.26, BIC = 6767.19). Opioid trajectories differed in the total amount of opioids consumed and the rate of opioid intake over the acute postoperative period. Intraoperative epimorphine dose predicted the opioid trajectory membership (p = 0.0498). Opioid trajectory groups were significantly associated with pain at 6 weeks (p = 0.0103) and 6 months (p = 0.0457) after surgery. Intraoperative epimorphine dose predicts the opioid consumption in the acute postoperative period. Opioid consumption during this period is associated with long-term pain. Understanding the acute postoperative period and its association with baseline predictors and long-term patient outcomes will allow for personalized perioperative care.
(274) Novel Neurosteroid Intervention for Chronic Low Back Pain in Iraq/Afghanistan-Era Veterans J. Naylor, J. Kilts, R. Wagner, L. Shampine, G. Parke, S. Szabo, and C. Marx; Durham VA Medical Center, Durham, NC Chronic low back pain symptoms are extremely common among Iraq/Afghanistan-era Veterans. However, pharmacological management for pain is frequently suboptimal, and many Veterans experience persistent and unalleviated pain symptoms and/or intolerable side effects to pain medications. Current medications such as opioids that are frequently used to treat chronic pain symptoms have side effect risks such as respiratory depression, addiction, sedation, and potentially lethal interactions with other drugs. There is thus an acute and immediate need for the development of effective, safe, and non-habit-forming pharmacological treatments for chronic pain disorders. Neurosteroids are endogenous molecules that are enriched in human brain and hold promise for pain therapeutics. Data in rodent models demonstrate that neurosteroids exhibit pronounced analgesic actions, and our data in Iraq/Afghanistan-era Veterans suggest that neurosteroids are decreased in the setting of pain symptoms in clinical populations. Neurosteroids are hence logical candidates for pain alleviation and have not been tested yet for this indication. We thus conducted a 6-week randomized, double-blind, placebo-controlled trial of pregnenolone versus placebo to determine if adjunctive pregnenolone has therapeutic utility for the treatment of chronic low back pain in Iraq/Afghanistan-era Veterans. The primary outcome measure was average pain intensity ratings from a daily pain diary. Secondary outcomes included pain interference scores. Pregnenolone was extremely well-tolerated. Veterans randomized to pregnenolone reported significant reductions in low back pain relative to those randomized to placebo (pain diary p=0.024; pain recall p=0.010). Pain interference scores for “work” (p=0.040) and “activity” (p=0.031) were also improved in Veterans randomized to pregnenolone compared to placebo. Pregnenolone may thus represent a new intervention for pain conditions that is safe, well-tolerated, non-habit-forming, and potentially efficacious for the alleviation of pain symptoms in Iraq/Afghanistan-era Veterans.
The Journal of Pain
S43
(275) Somatosensory Predictors of Response to Pregabalin in Painful Chemotherapy-Induced Peripheral Neuropathy (CIPN): A Randomized, Placebo-Controlled, Crossover Study A. Hincker, K. Frey, L. Rao, N. Wagner-Johnston, A. Abdallah, B. Tan, M. Amin, T. Wildes, R. Shah, K. Bakos, P. Kalsson, and S. Haroutounian; Washington University, St. Louis, MO Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of a2d subunits of voltage-gated Ca2+ channels, such as pregabalin, have shown efficacy in reducing mechanical hypersensitivity in animal models of neuropathic pain. In addition, some data suggested that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased hypersensitivity to pinprick. We hypothesized that mechanical hypersensitivity, as quantified by decreased mechanical pain threshold (MPT) at the dorsal feet, would be predictive of a greater reduction in average daily pain in response to pregabalin versus placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600mg a day) and placebo in cross-over design. Twenty-three participants completed both arms and were eligible for efficacy analysis. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, p = 0.23) or worst pain (29.2% vs 16.0%, p = 0.13) from baseline. Post-hoc analysis of patients with CIPN caused by oxaliplatin only (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, p = 0.04). MPT was not significantly correlated with reduction in average pain (p = 0.20) or worst pain (p = 0.19) in response to pregabalin. In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN. This work was supported by the ASPIRE grant program by Pfizer, Inc.
(276) Acute Exercise Decreases Situational Pain Catastrophizing of a Noxious Stimulus R. Nevsimal, A. Awali, A. Alsouhibani, S. O’Melia, and M. Hoeger Bement; Marquette University, Milwaukee, WI There is limited evidence regarding the variability in pain response following exercise, including the impact of pain catastrophizing. The purpose of this study was to investigate the relation of the pain response after exercise with pain catastrophizing levels in young healthy individuals. Fifty-seven participants (20.75§1.81 years, 29 women) completed two randomized sessions (exercise and quiet rest). Exercise consisted of sustained submaximal isometric contraction of the knee extensors, performed until task failure. Temporal summation (TS) was assessed before and after exercise and quiet rest, by applying a constant mechanical stimulus to the index finger for one minute after reported pain threshold. During the one minute, participants were asked to rate their pain every 15 seconds (0-10 Numerical Pain Rating Scale). TS was calculated as the last pain rating minus the first pain rating. Pain catastrophizing scale (PCS) was completed at the beginning of the first session. Situational catastrophizing (S-PCS) was completed after each TS protocol. Based on the change in pain following exercise, participants were divided into two groups, responders (hypoalgesia) and nonresponders (no change or hyperalgesia). There was no difference in baseline PCS between groups (p=0.974). For S-PCS, there was a session x trial x group interaction (p<0.001). In the exercise session, responders had a reduction in S-PCS (p=0.001) while S-PCS increased in the non-responders (p=0.018). In the quiet rest session, S-PCS did not change (p=0.365). There was a significant correlation between the change in S-PCS and TS with exercise (r= 0.31, p=0.02) after controlling for the effect of baseline S-PCS and TS. Exercise impacts both central pain modulation and psychological attributes related to pain. This study provides further support for the integration of psychological and physiological aspects of nonpharmacological pain management with exercise interventions.
(277) Racial/Ethnic Disparities in Opioid Prescribing for LongBone Fractures at Emergency Department Discharge: A CrossSectional Analysis of 22 Centers from a Single Healthcare Delivery System R. Romanelli, Z. Shen, N. Szwerinski, A. Scott, and A. Pressman; Palo Alto Medical Foundation Research Institute, Palo Alto, CA