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Human induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) and human dorsal root ganglia neurons (hDRG-N) are popular tools in the field of pain research; however, few groups make use of both approaches. For screening and analgesic validation purposes, important characterizations can be determined of the similarities and differences between hDRG-N and hiPSC-SNs. This study focuses specifically on the electrophysiology properties of hDRG-N in comparison to hiPSC-SNs. We also compared hDRG-N and hiPSC-SNs from both male and female donors to evaluate potential sex differences. We recorded neuronal size, rheobase, resting membrane potential, input resistance, and action potential waveform properties from 83 hiPSCs-SNs (2 donors) and 108 hDRG-N neurons (8 donors). We observed several statistically significant electrophysiological differences between hDRG-N and hiPSC-SNs, such as size, rheobase, input resistance, and several action potential waveform properties. Correlation analysis also revealed many properties that were positively or negatively correlated, some of which were differentially correlated between hDRG-N and hiPSC-SNs. This study shows several differences between hDRG-N and hiPSC-SNs and allows a better understanding of the advantages and disadvantages of both for use in pain research. We hope this study will be a valuable resource for pain researchers considering the use of these human in vitro systems for mechanistic studies and/or drug development projects. PERSPECTIVE: hiPSC-SNs and hDRG-N are popular tools in the field of pain research. This study allows for a better functional understanding of the pros and cons of both tools., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Human induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) and human dorsal root ganglia (hDRG) neurons are popular tools in the field of pain research; however, few groups make use of both approaches. For screening and analgesic validation purposes, important characterizations can be determined of the similarities and differences between hDRG and hiPSC-SNs. This study focuses specifically on electrophysiology properties of hDRG in comparison to hiPSC-SNs. We also compared hDRG and hiPSC-SNs from both male and female donors to evaluate potential sex differences. We recorded neuronal size, rheobase, resting membrane potential, input resistance, and action potential waveform properties from 83 hiPSCs-SNs (2 donors) and 108 hDRG neurons (9 donors). We observed several statistically significant electrophysiological differences between hDRG and hiPSC-SNs, such as size, rheobase, input resistance, and several actional potential (AP) waveform properties. Correlation analysis also revealed many properties that were positively or negatively correlated, some of which were differentially correlated between hDRG and hiPSC-SNs. This study shows several differences between hDRG and hiPSC-SNs and allows better understanding of the advantages and disadvantages of both for use in pain research. We hope this study will be a valuable resource for pain researchers considering the use of these human in vitro systems for mechanistic studies and/or drug development projects.

Dynorphin A (1-17) (DynA17) has been identified as a key regulator of both sensory and affective dimensions of chronic pain. Following nerve injury, increases in DynA17 have been reported in the spinal and supraspinal areas involved in chronic pain. Blocking these increases provides therapeutic benefits in preclinical chronic pain models. Although heavily characterized at the behavioral level, how DynA17 mediates its effects at the cellular physiological level has not been investigated. In this report, we begin to decipher how DynA17 mediates its direct effects on mouse dorsal root ganglion (DRG) cells and how intrathecal administration modifies a key node in the pain axis, the periaqueductal gray These findings build on the plethora of literature defining DynA17 as a critical neuropeptide in the pathophysiology of chronic pain syndromes.

Background: Co-prescribing of scheduled drugs is endemic in the United Sates, increasing health risks to patients and the burden on healthcare systems., Purpose: We conducted a pragmatic historical cohort study to measure the effect of enrollment in a state-authorized United States' Medical Cannabis Program (MCP) on scheduled II-V drug prescription patterns., Procedures: Eighty-three chronic pain patients, who enrolled in the New Mexico MCP between April 1, 2010 and October 3, 2015, were compared with 42 nonenrolled patients over a 24-month period (starting 6 months before enrollment for the MCP patients) using the Prescription Monitoring Program. The outcome variables include baseline levels and pre- and postenrollment monthly trends in the number of drug prescriptions, distinct drug classes, dates prescription drugs were filled, and prescribing providers., Findings: Twenty-eight MCP patients (34%) and 1 comparison group patient (2%) ceased the use of all scheduled prescription medications by the last 6 months of the observation period. Age- and sex-adjusted regressions show that, although no statistically significant differences existed in pre-enrollment levels and trends, the postenrollment trend among MCP patients is statistically significantly negative for all 4 measures (decreases in counts of -0.02 to -0.04, P values between <.001 and .017), whereas the postenrollment trend is 0 among the comparison group. Controlling for time-invariant patient characteristics suggested that MCP patients showed statistically significantly lower levels across all 4 measures by 10 months postenrollment., Conclusions: Legal access to cannabis may reduce the use of multiple classes of dangerous prescription medications in certain patient populations., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Current levels and dangers of opioid use in the U.S. warrant the investigation of harm-reducing treatment alternatives., Purpose: A preliminary, historical, cohort study was used to examine the association between enrollment in the New Mexico Medical Cannabis Program (MCP) and opioid prescription use., Methods: Thirty-seven habitual opioid using, chronic pain patients (mean age = 54 years; 54% male; 86% chronic back pain) enrolled in the MCP between 4/1/2010 and 10/3/2015 were compared to 29 non-enrolled patients (mean age = 60 years; 69% male; 100% chronic back pain). We used Prescription Monitoring Program opioid records over a 21 month period (first three months prior to enrollment for the MCP patients) to measure cessation (defined as the absence of opioid prescriptions activity during the last three months of observation) and reduction (calculated in average daily intravenous [IV] morphine dosages). MCP patient-reported benefits and side effects of using cannabis one year after enrollment were also collected., Results: By the end of the 21 month observation period, MCP enrollment was associated with 17.27 higher age- and gender-adjusted odds of ceasing opioid prescriptions (CI 1.89 to 157.36, p = 0.012), 5.12 higher odds of reducing daily prescription opioid dosages (CI 1.56 to 16.88, p = 0.007), and a 47 percentage point reduction in daily opioid dosages relative to a mean change of positive 10.4 percentage points in the comparison group (CI -90.68 to -3.59, p = 0.034). The monthly trend in opioid prescriptions over time was negative among MCP patients (-0.64mg IV morphine, CI -1.10 to -0.18, p = 0.008), but not statistically different from zero in the comparison group (0.18mg IV morphine, CI -0.02 to 0.39, p = 0.081). Survey responses indicated improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few side effects from using cannabis one year after enrollment in the MCP (ps<0.001)., Conclusions: The clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrants further investigations on cannabis as a potential alternative to prescription opioids for treating chronic pain.

Objectives: To investigate the effectiveness of telephone counselling as an adjunct to nicotine replacement therapy (NRT) by transdermal patch in smoking cessation., Design: Randomised controlled trial., Participants and Setting: 854 smokers from New South Wales, aged 18 years and older, who had smoked at least 10 cigarettes per day for the past year and responded to newspaper advertisements between October 2001 and January 2002; the trial was conducted between October 2001 and August 2002., Interventions: Random allocation to either NRT alone or NRT plus telephone counselling (5 sessions spaced according to a relapse-sensitive call schedule)., Main Outcome Measures: Self-reported abstinence assessed by telephone questionnaires at 1, 2, 3 and 6 months: 28-day continuous abstinence at 3 and 6 months, and 90-day continuous abstinence at 6 months., Results: 28-day continuous abstinence rates among participants receiving telephone counselling were significantly greater than among those not receiving telephone counselling at both 3 and 6 months (31.6% v 25.1%; P = 0.04 at 3 months; and 30.1% v 22.4%; P = 0.01 at 6 months). Similarly, 90-day continuous abstinence rates at 6 months were significantly greater for participants receiving counselling (26.7% v 18.6%; P = 0.004)., Conclusion: Telephone counselling as an adjunct to NRT increases abstinence rates beyond the use of NRT alone.

Plasticity of the synaptic contact zone was previously observed following loss of synapses in the cerebral cortex of normal aging humans. The present study was undertaken to determine if there was quantitative evidence of synapse loss and synapse plasticity in the inferior temporal, superior parietal, parieto-occipital, and superior frontal cortical regions in Alzheimer's disease (AD), and how such changes related to the neurofibrillary tangles and amyloid plaques. The results showed that age at autopsy did not correlate with the numbers of synapses, plaques, or tangles. However, the numbers of synapses strongly reflected the pathology of AD; in all four brain regions, there were fewer synapses as the numbers of plaques and tangles increased. In the inferior temporal and superior parietal cortices, the loss of synapses was accompanied by an increase in the synaptic contact length. The results suggest that, in some cerebral cortical brain regions, synapses are capable of plasticity changes, even when the pathology of AD and loss of synapses are severe.