Postmortem toxicology findings from the Camden Opioid Research Initiative.

The United States continues to be impacted by decades of an opioid misuse epidemic, worsened by the COVID-19 pandemic and by the growing prevalence of highly potent synthetic opioids (HPSO) such as fentanyl. In instances of a toxicity event, first-response administration of reversal medications such as naloxone can be insufficient to fully counteract the effects of HPSO, particularly when there is co-occurring substance use. In an effort to characterize and study this multi-faceted problem, the Camden Opioid Research Initiative (CORI) has been formed. The CORI study has collected and analyzed post-mortem toxicology data from 42 cases of decedents who expired from opioid-related toxicity in the South New Jersey region to characterize substance use profiles. Co-occurring substance use, whether by intent or through possible contamination of the illicit opioid supply, is pervasive among deaths due to opioid toxicity, and evidence of medication-assisted treatment is scarce. Nearly all (98%) of the toxicology cases show the presence of the HPSO, fentanyl, and very few (7%) results detected evidence of medication-assisted treatment for opioid use disorder, such as buprenorphine or methadone, at the time of death. The opioid toxicity reversal drug, naloxone, was detected in 19% of cases, but 100% of cases expressed one or more stimulants, and sedatives including xylazine were detected in 48% of cases. These results showing complex substance use profiles indicate that efforts at mitigating the opioid misuse epidemic must address the complications presented by co-occurring stimulant and other substance use, and reduce barriers to and stigmas of seeking effective medication-assisted treatments.

Patient Perceptions and Potential Utility of Pharmacogenetic Testing in Chronic Pain Management and Opioid Use Disorder in the Camden Opioid Research Initiative.

Pharmacogenetics (PGx) has the potential to improve opioid medication management. Here, we present patient perception data, pharmacogenetic data and medication management trends in patients with chronic pain (arm 1) and opioid use disorder (arm 2) treated at Cooper University Health Care in Camden City, NJ. Our results demonstrate that the majority of patients in both arms of the study (55% and 65%, respectively) are open to pharmacogenetic testing, and most (66% and 69%, respectively) believe that genetic testing has the potential to improve their medical care. Our results further support the potential for CYP2D6 PGx testing to inform chronic pain medication management for poor metabolizers (PMs) and ultrarapid metabolizers (UMs). Future efforts to implement PGx testing in chronic pain management, however, must address patient concerns about genetic test result access and genetic discrimination.

The Genomics of Opioid Addiction Longitudinal Study (GOALS): study design for a prospective evaluation of genetic and non-genetic factors for development of and recovery from opioid use disorder.

BACKGROUND: The opioid use disorder and overdose crisis in the United States affects public health as well as social and economic welfare. While several genetic and non-genetic risk factors for opioid use disorder have been identified, many of the genetic associations have not been independently replicated, and it is not well understood how these factors interact. This study is designed to evaluate relationships among these factors prospectively to develop future interventions to help prevent or treat opioid use disorder. METHODS: The Genomics of Opioid Addiction Longitudinal Study (GOALS) is a prospective observational study assessing the interplay of genetic and non-genetic by collecting comprehensive genetic and non-genetic information on 400 participants receiving medication for opioid use disorder. Participants will be assessed at four time points over 1 year. A saliva sample will be collected for large-scale genetic data analyses. Non-genetic assessments include validated surveys measuring addiction severity, depression, anxiety, and adverse childhood experiences, as well as treatment outcomes such as urine toxicology results, visit frequency, and number of pre and post-treatment overdoses extracted from electronic medical records. DISCUSSION: We will use these complex data to investigate the relative contributions of genetic and non-genetic risk factors to opioid use disorder and related treatment outcomes.

The importance of medical education in the changing field of pain medicine.

Suffering chronic pain is a global epidemic that requires a closer look on how we are educating trainees to become more effective in pain management. The vast majority of medical professionals will encounter treatment of pain throughout their career. Our current system for educating these medical professionals is flawed in a number of ways. Improving pain education will narrow the gap between over and under treatment of acute and chronic pain. Reviews have demonstrated dissatisfaction among practitioners throughout the world on how pain education is currently conducted. Changing the educational process will require support from several areas: medical educators, clinicians, policymakers, administrators and several other organizations.

Advances in translational neuropathic research: example of enantioselective pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief in complex regional pain syndrome.

Historically, complex regional pain syndrome (CRPS) was poorly defined, which meant that scientists and clinicians faced much uncertainty in the study, diagnosis, and treatment of the syndrome. The problem could be attributed to a nonspecific diagnostic criteria, unknown pathophysiologic causes, and limited treatment options. The two forms of CRPS still are painful, debilitating disorders whose sufferers carry heavy emotional burdens. Current research has shown that CRPS I and CRPS II are distinctive processes, and the presence or absence of a partial nerve lesion distinguishes them apart. Ketamine has been the focus of various studies involving the treatment of CRPS; however, currently, there is incomplete data from evidence-based studies. The question as to why ketamine is effective in controlling the symptoms of a subset of patients with CRPS and not others remains to be answered. A possible explanation to this phenomenon is pharmacogenetic differences that may exist in different patient populations. This review summarizes important translational work recently published on the treatment of CRPS using ketamine.

Deep cervical plexus block for the treatment of cervicogenic headache.

BACKGROUND: Cervicogenic headache descriptors include its unilateral nature, "signs and symptoms linking it to the neck," and trauma of the neck. Since the pain often occurs over the C2 or C3 nerve root, we used a modification of the deep cervical block technique for treatment of this refractory type headache. OBJECTIVE: To determine the efficacy of a modified deep cervical block for treatment of cervicogenic headache. DESIGN: Prospective case study. METHODS: Thirty-nine patients referred to our pain clinic participated in this study. All patients had undergone extensive screening/diagnostic testing. The blocks were performed unilaterally, without inducing a risk of invading the neural foramen, and repeat injection of the contra-lateral side occurred at >1 week after initial injection. Patients were followed for a 6-month period using a pain diary and questionnaire. Pain was assessed pre- and post-injection and 3 and 6 months post treatments. RESULTS: The mean treatment period was 59 +/- 61 days. The mean values for pre- and post-injection series pain scores (0-10 pain scale) were 9.54 +/- 1.53 and 6.75 +/- 3.23 respectively (p <0.001). Thirty-three percent (33%) of the patients reported pain scores of < or = 4 on the 0-10 pain scale after their last treatment. Effectiveness of the therapy following the injection procedure was rated to be 42% effective for all first injections and 40% effective for last injections (p =NS). Six months evaluations showed that return of moderate to severe pain took 6.62 +/- 8.1 weeks. At the 3 and 6 months follow up evaluations, mean pain scores had returned to 8.41 +/- 2.96 and 8.83 +/- 2.78, respectively. Ten patients (24%) had pain scores < or = 4 at the 3-month evaluation while 7 of the patients (18%) had pain scores < or = 4 at the 6-month evaluation. CONCLUSIONS: These results showed that for some patients this series of blocks provided effective pain relief for 3 months post treatment but by 6 months the pain had returned to pre-treatment levels. This block technique significantly diminished pain after the initial as well as the last treatment. These clinically significant changes in pain relief suggest that more aggressive selective therapy targeting these nerve routes might provide longer lasting relief.