Repeated dextromethorphan administration in adolescent rats produces long-lasting behavioral alterations.

Initiation of non-medical dextromethorphan (DXM) use often occurs in adolescence, yet little is known about the consequences when use begins during this developmental period. The current experiments examined the acute response and the effects of repeated exposure to DXM in adolescence on behavior in adulthood. We examined locomotor activity, locomotor sensitization, and cognitive function, in rats that received repeated administration of DXM. Groups of adolescent (PND 30) and adult (PND 60) male rats were treated with DXM (60 mg/kg) once daily for 10 days. Locomotor activity in response to DXM was assessed following the first injection, on the 10th day of injection (adolescent - PND 39; adult - PND 69), and following 20 days of abstinence (adolescent - PND 59; adult - PND 89). Acute locomotor effects and locomotor sensitization were compared in adolescents and adults; cross-sensitization to ketamine, another dissociative with abuse potential, was also examined. In a separate group of rodents cognitive deficits were assessed following a 20 day abstinence period (adolescent - PND 59; adult - PND 89) in spatial learning and novel object recognition tasks. The locomotor stimulant effect of DXM was much greater in adolescents than adults. Also, only adolescent rats that were repeatedly administered DXM demonstrated locomotor sensitization at the end of 10 days of injection. However, sensitization occurred after the abstinence period in all rats regardless of age. Nonetheless, cross-sensitization to ketamine was only evident in adolescent-treated rats. DXM also led to an increase in perseverative errors in reversal learning only in the adolescent-treated group. We conclude that repeated use of DXM produces long-lasting neuroadaptations that may contribute to addiction. Deficits in cognitive flexibility occur in adolescents, although further work is necessary to confirm these findings. The results extend the understanding of potential long-term consequences of DXM use in adolescents and adults.

Technology-based communication among Hurricane Maria survivors in the United States: a trans-territorial lens.

PURPOSE: Rooted in a trans-territorial framework, the present study was designed to provide new evidence regarding the patterns of communication among Hurricane Maria survivors who migrated to the U.S. in the aftermath of the storm. METHODS: A total of 319 Hurricane Maria survivor adults ages 18 and older were recruited into the Adelante Boricua study between August 2020 and October 2021. Most participants had relocated to the U.S. between 2017 and 2018. We used latent profile analysis and multinomial regression to examine the relationship of technology-based communication with depressive symptoms, well-being, cultural connection, and migration stress. RESULTS: We identified a five-class solution, consisting of (1) moderate communication (32%), (2) disengaged (24%), (3) no social media (18%), (4) daily with family in Puerto Rico (6%), and (5) daily trans-territorial (13%) typologies. Participants in the disengaged class were more likely to report elevated depressive symptoms and limited English proficiency, lower prosocial behaviors, lower levels of religiosity, lower attendance at religious services in the U.S., and less engagement in social activities, compared to participants in the Moderate Communication class. CONCLUSION: Roughly one in four individuals in our sample reported very limited technology-based communication with friends/family in their sending and new-receiving communities. As technology and smartphones continue to become integrated into 21st-century life, it is vital that researchers explore how the tremendous potential for connectedness relates to trans-territorial crisis migrants' well-being and adaptation.

Amplifying the Patient Voice: A Survey of Practitioners' Use of Patient-reported Outcome Measures Across Radiotherapy Providers in England.

AIMS: The NHS England Radiotherapy Service Specification calls for routine use of patient-reported outcome measures (PROMs). However, barriers exist at patient, healthcare professional and service levels. The aim of the present study was to determine the current use of PROMs within radiotherapy services in England. The current attitudes, barriers and enablers to the implementation of PROMs in radiotherapy practice were evaluated and practical recommendations to inform future implementation were developed. MATERIALS AND METHODS: A mixed-methods approach was adopted to obtain quantitative and qualitative data. An online questionnaire was developed and disseminated to all radiotherapy operational delivery network managers across England. The questionnaire consisted of 12 open and closed questions relating to PROMs use, with the option to provide free-text responses. Inductive thematic analysis was conducted on free-text comments, whereas descriptive statistics were used to analyse quantitative data. RESULTS: In total, 182 responses were received from 40 of the 50 radiotherapy providers, resulting in a response rate of 84%. The current use of PROMs was analysed, including rationale for use, tools used, format of PROMs collection and timing within the radiotherapy pathway. Most respondents indicated that PROMs were used in the context of clinical trials only. Through thematic analysis, four identical key themes were identified relating to both barriers and enablers to PROMs use; these included IT infrastructure, time, human/financial resources and training/education. A fifth theme, standardisation, was identified as a key enabler to PROMs use. CONCLUSIONS: Our findings show that outside of clinical trials, PROMs are not routinely used in radiotherapy services due to barriers identified at professional and service levels. Here we provide recommendations to mitigate the barriers identified and implement PROMs in radiotherapy, including training for healthcare professionals and standardisation of PROMs tools and storage. This study provides a key first step in driving PROMs implementation within radiotherapy services across England.

Sex-specific alterations in corticotropin-releasing factor regulation of coerulear-cortical network activity.

The locus coeruleus (LC)-norepinephrine system is a stress responsive system that regulates arousal and cognitive functions through extensive projections, including to the prefrontal cortex. LC-cortical circuits are activated by stressors, and this activation is thought to contribute to stress-induced impairments in executive function. Because corticotropin-releasing factor (CRF) is a mediator of stress-induced LC activation, we examined the effects of CRF administered into the LC of male and female rats on network activity of two functionally distinct regions of the PFC, the medial PFC (mPFC) and the orbitofrontal cortex (OFC). Network activity, measured as local field potentials, was recorded in awake animals before and after intra-LC infusion of aCSF or CRF (2 or 20 ng). CRF had qualitatively distinct effects on network activity in males and females with respect to dose, region and timecourse. CRF (20 ng) produced a prominent theta oscillation (7-9 Hz) selectively in female rats shortly after LC infusion and 20 min later. In contrast, in male rats, CRF (2 and 20 ng) decreased the amplitude of power in the 4-6 Hz range in the mPFC 10 min after injection. Lastly, CRF (20 ng) increased mPFC-OFC coherence in females and decreased mPFC-OFC coherence in males. In sum, these results show sex differences in CRF modulation of the LC-norepinephrine system that regulates prefrontal cortical networks, which may underlie sex differences in cognitive and behavioral responses to stress.

ESR1, PGR, ERBB2, and MKi67 mRNA expression in postmenopausal women with hormone receptor-positive early breast cancer: results from ABCSG Trial 6.

BACKGROUND: The purpose of this study was to assess the concordance of real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) detection of ESR1, PGR, ERBB2, and MKi67 messenger RNA (mRNA) in breast cancer tissues with central immunohistochemistry (IHC) in women treated within the prospective, randomized Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6. PATIENTS AND METHODS: We evaluated ESR1, PGR, ERBB2, and MKi67 mRNA expression by Xpert® Breast Cancer STRAT4 (enables cartridge-based RT-qPCR detection of mRNA in formalin-fixed paraffin-embedded tissues) and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 protein expression by IHC [in situ hybridization (ISH) for HER2 IHC 2+] in 1115 surgical formalin-fixed paraffin-embedded specimens from patients of ABCSG Trial 6. Overall percent agreement (concordance), positive percent agreement (sensitivity), and negative percent agreement (specificity) between STRAT4 and IHC were determined for each marker. The primary objective of the study was concordance between STRAT4 mRNA measurements of ESR1, PGR, ERBB2, and MKi67 with central reference laboratory IHC (and ISH for HER2 IHC 2+ cases). Time to distant recurrence was analyzed by Cox models. RESULTS: All performance targets for ER, PR, and Ki67 were met. For HER2, the negative percent agreement target but not the positive percent agreement target was met. Concordance between STRAT4 and IHC was 98.9% for ER, 89.9% for PR, 98.2% for HER2, and 84.8% for Ki67 (excluding intermediate IHC 10%-20% staining). In univariable and multivariable Cox regression analyses, all four biomarkers tested by either STRAT4 RT-qPCR or by central IHC (ISH) had a comparable time to distant recurrence indicating similar prognostic value. CONCLUSIONS: With the exception of HER2, we demonstrate high concordance between centrally assessed IHC and mRNA measurements of ER, PR, and Ki67 as well as a high correlation of the two methods with clinical outcome. Thus, mRNA-based assessment by STRAT4 is a promising new tool for diagnostic and therapeutic decisions in breast cancer.

Use and abuse of dissociative and psychedelic drugs in adolescence.

Adolescence is a period of profound developmental changes, which run the gamut from behavioral and neural to physiological and hormonal. It is also a time at which there is an increased propensity to engage in risk-taking and impulsive behaviors like drug use. This review examines the human and preclinical literature on adolescent drug use and its consequences, with a focus on dissociatives (PCP, ketamine, DXM), classic psychedelics (LSD, psilocybin), and MDMA. It is the case for all the substances reviewed here that very little is known about their effects in adolescent populations. An emerging aspect of the literature is that dissociatives and MDMA produce mixed reinforcing and aversive effects and that the balance between reinforcement and aversion may differ between adolescents and adults, with consequences for drug use and addiction. However, many studies have failed to directly compare adults and adolescents, which precludes definitive conclusions about these consequences. Other important areas that are largely unexplored are sex differences during adolescence and the long-term consequences of adolescent use of these substances. We provide suggestions for future work to address the gaps we identified in the literature. Given the widespread use of these drugs among adolescent users, and the potential for therapeutic use, this work will be crucial to understanding abuse potential and consequences of use in this developmental stage.

Air pollution interventions and respiratory health: a systematic review.

BACKGROUND: Indoor and ambient air pollution exposure is a major risk to respiratory health worldwide, particularly in low- and middle-income countries (LMICs). Interventional trials have mainly focused on alternatives to cooking stoves, with mixed results. Beyond cooking, additional sources of particulate matter also contribute to the burden of air pollution exposure. This review explores evidence from current randomised controlled trials (RCTs) on the clinical effectiveness of interventions to reduce particulate matter in LMICs.METHODS: Twelve databases and the grey literature (e.g., Government reports and policy papers) were searched. Eligible studies were RCTs conducted in LMICs aiming to reduce particulate exposure from any source and reporting on at least one clinical respiratory outcome (respiratory symptoms, lung function or clinical diagnoses). Data from relevant studies were systematically extracted, the risk of bias assessed and narrative synthesis provided.RESULTS: Of the 14 included studies, 12 tested 'improved' cookstoves, most using biomass, but solar and bioethanol cookers were also included. One trial used solar lamps and another was an integrated intervention incorporating behavioural and environmental components for the treatment and prevention of chronic obstructive pulmonary disease. Of the six studies reporting child pneumonia outcomes, none demonstrated significant benefit in intention-to-treat analysis. Ten studies reported respiratory symptom outcomes with some improvements seen, but self-reporting made these outcomes highly vulnerable to bias. Substantial inter-study clinical and methodological heterogeneity precluded calculation of pooled effect estimates.CONCLUSION: Evidence from the RCTs performed to date suggests that individual household-level interventions for air pollution exposure reduction have limited benefits for respiratory health. More comprehensive approaches to air pollution exposure reduction must be developed so their potential health benefits can be assessed.

Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance.

The exact biological mechanism governing the radioresistant phenotype of prostate tumours at a high risk of recurrence despite the delivery of advanced radiotherapy protocols remains unclear. This study analysed the protein expression profiles of a previously generated isogenic 22Rv1 prostate cancer model of radioresistance using DigiWest multiplex protein profiling for a selection of 90 signalling proteins. Comparative analysis of the profiles identified a substantial change in the expression of 43 proteins. Differential PARP-1, AR, p53, Notch-3 and YB-1 protein levels were independently validated using Western Blotting. Pharmacological targeting of these proteins was associated with a mild but significant radiosensitisation effect at 4Gy. This study supports the clinical relevance of isogenic in vitro models of radioresistance and clarifies the molecular radiation response of prostate cancer cells.

Long-lasting effects of repeated ketamine administration in adult and adolescent rats.

Initiation of ketamine use often occurs in adolescence, yet little is known about long-term consequences when use begins in this developmental period. The current experiments were designed to examine the effects of repeated exposure to ketamine in adolescence on behavior in adulthood. We examined locomotor activity, as well as cognitive function, in animals that received repeated administration of ketamine. Groups of adolescent and adult male rats were treated with ketamine (25 mg/kg) once daily for 10 days. Locomotor activity was assessed following the first injection, following 10 days of injection, and following 20 days of abstinence. Acute locomotor effects and locomotor sensitization were compared in adolescents and adults; cross-sensitization to dextromethorphan, another dissociative with abusive potential, was also examined. In a separate group of animals cognitive deficits were assessed following the 20 day abstinence period in spatial learning and novel object recognition tasks. The locomotor stimulant effect of ketamine was much greater in adolescents than adults. Animals that were repeatedly administered ketamine demonstrated locomotor sensitization immediately after the final injection. However, sensitization only persisted after the abstinence period in animals treated as adults. No cross-sensitization to dextromethorphan was evident. Ketamine failed to produce statistically significant cognitive deficits in either age group, although drug-treated adults showed a trend towards deficits in spatial learning. Repeated use of ketamine produces long-lasting neuroadaptations that may contribute to addiction. Mild lasting memory deficits may occur in adults, although further work is necessary to confirm these findings. The results extend the understanding of potential long-term consequences of ketamine use in adolescents and adults.

Household concepts of wellbeing and the contribution of palliative care in the context of advanced cancer: A Photovoice study from Blantyre, Malawi.

INTRODUCTION: Cancer and other life-limiting non-communicable diseases are on the increase in Africa affecting younger populations frequently diagnosed at an advanced stage of disease. The United Nations Sustainable Development Goal 3 aims for 'healthy life and wellbeing for all at all ages', though there is a limited understanding of wellbeing particularly from patients' and families' perspectives in these populations. Palliative care is an approach which aims to improve the quality of life for patients and families affected by life-limiting disease, though access to palliative care has been described as an issue which is 'largely ignored' on the global health agenda. The aim of this Photovoice study was to explore patient and family perspectives of wellbeing and the contribution of palliative care following a diagnosis of advanced cancer in Blantyre, Malawi. METHODS: Between November 2016 and February 2017, 13 co-researchers (6 patients receiving palliative care for advanced cancer and 7 un-paid family caregivers) gathered photographs to depict aspects of their daily lives. Participatory analysis was conducted and an advocacy event (including photographic exhibits) held. RESULTS: Wellbeing was described as seeing improvements in the patients' function facilitating inclusion in activities of daily living (including income generation) that had not previously been possible due to their illness. Family caregivers, neighbours and community members play a key role as 'courage givers' supported by health workers and religious groups, though discrimination in the form of social exclusion was also reported to be significant with patients expressing that they may be considered 'prematurely dead' in their community. Palliative care improves wellbeing by providing pain and symptom management enabling patients and / or family caregivers to return to household and income generating tasks. Through close interaction with households and ongoing counselling palliative care services assist to reduce fear and discrimination. CONCLUSIONS: To achieve Sustainable Development Goal 3 for patients and families affected by life limiting illnesses in low resource settings, further understanding of the frequency and impact of discrimination is required as well as improved access to palliative care.

The role of the vasopressin system and dopamine D1 receptors in the effects of social housing condition on morphine reward.

BACKGROUND: The association with opioid-abusing individuals or even the perception of opioid abuse by peers are risk factors for the initiation and escalation of abuse. Similarly, we demonstrated that morphine-treated animals housed with only morphine-treated animals (referred to as morphine only) acquire morphine conditioned place-preference (CPP) more readily than morphine-treated animals housed with drug-naïve animals (referred to as morphine cage-mates). However, the molecular mechanisms underlying these effects are still elusive. METHODS: Mice received repeated morphine or saline while housed as saline only, morphine only, or cage-mates. Then, they were examined for the expression levels of D1 dopamine receptor (D1DR), D2 dopamine receptor (D2DR), dopamine transporter (DAT), oxytocin, and Arginine-vasopressin (AVP) in the striatum using qPCR. Additionally, we examined the effects of the AVP-V1b receptor antagonist, SSR149415, on the acquisition of morphine conditioned place-preference (CPP). RESULTS: Increased striatal expression of D1DR and AVP was observed in morphine only animals, but not morphine cage-mates. No significant effects were observed on the striatal expression of D2DR, DAT, or oxytocin. Antagonizing the AVP-V1b receptors decreased the acquisition of morphine CPP in the morphine only mice, but did not alter the acquisition of morphine CPP in the morphine cage-mate mice. CONCLUSIONS: Housing with drug-naïve animals protects against the increase in striatal expression of D1DR and AVP elicited by morphine exposure. Moreover, our studies suggest that the protective effect of housing with drug-naïve animals on the acquisition of morphine reward might be, at least partially, mediated by AVP.

Chlorinated persistent organic pollutants in serum of New Zealand adults, 2011-2013.

A national survey was conducted in 2011-2013 to assess serum concentrations of persistent organic pollutants (POPs) in adult New Zealanders. Participants were randomly selected from the 2010 Electoral Roll within 64 demographic strata according to 4 age groups, 4 regions, 2 ethnic groups (Maori/non-Maori) and gender. Eligible subjects (n=734) donated up to 30ml of blood, after which serum was pooled (n=49) according to demographic strata prior to analysis by GC-HRMS. Associations between demographic variables (age, region, ethnicity, gender) and serum POPs were assessed using linear regression. The weighted geometric mean (GM) of PCDD/Fs was 5.3pg/g lipid toxic equivalents using the WHO 2005 toxic equivalence factors (TEQ05), which increased by age (3.2, 4.4, 4.8, and 8.1pg/g lipid for the 19-24, 25-34, 35-49, and 50-64year age groups, respectively). The weighted GM of dioxin-like PCBs was 1.4pg TEQ05/g lipid which also increased by age (0.82, 0.86, 1.4, and 2.3pg/g lipid for the same age groups, respectively). Of the detected OCPs, the highest concentration was observed for p,p'-DDE (weighted GM, 220ng/g lipid) followed by hexachlorobenzene (HCB; 7.3ng/g lipid), beta-HCH (7.0ng/g lipid), and dieldrin (4.7ng/g lipid). For most Cl-POPs, concentrations were lowest in the youngest age group, and were similar for men and women and Maori and non-Maori. Serum Cl-POPs were, on average, 50% lower than those measured 15years earlier in 1997. This survey provides evidence of declining serum concentrations of chlorinated POPs in the New Zealand adult population. Age was the most important determinant of POPs concentrations. Body burdens of PCDD/Fs and PCBs in New Zealand are relatively low by international comparison, while for OCPs they are similar or lower compared to those reported for other developed countries.

Exposure reductions associated with introduction of solar lamps to kerosene lamp-using households in Busia County, Kenya.

Solar lamps are a clean and potentially cost-effective alternative to polluting kerosene lamps used by millions of families in developing countries. By how much solar lamps actually reduce exposure to pollutants, however, has not been examined. Twenty households using mainly kerosene for lighting were enrolled through a secondary school in Busia County, Kenya. Personal PM2.5 and CO concentrations were measured on a school pupil and an adult in each household, before and after provision of 3 solar lamps. PM2.5 concentrations were measured in main living areas, pupils' bedrooms, and kitchens. Usage sensors measured use of kerosene and solar lighting devices. Ninety percent of baseline kerosene lamp use was displaced at 1-month follow-up, corresponding to average PM2.5 reductions of 61% and 79% in main living areas and pupils' bedrooms, respectively. Average 48-h exposure to PM2.5 fell from 210 to 104 µg/m3 (-50%) among adults, and from 132 to 35 µg/m3 (-73%) among pupils. Solar lamps displaced most kerosene lamp use in at least the short term. If sustained, this could mitigate health impacts of household air pollution in some contexts. Achieving safe levels of exposure for all family members would likely require also addressing use of solid-fuel stoves.

Inhibiting social support from massage-like stroking increases morphine dependence.

Our previous studies showed that altering solely the drug experience of the cage mates with which rodents are housed affects the development of morphine dependence. In this study, we used designer receptors exclusively activated by designer drugs to artificially increase or decrease the activity of peripheral dorsal root ganglia sensory neurons expressing the G-protein-coupled receptor MRGPRB4. This is because sensory MRGPRB4-expressing neurons were shown to specifically detect the sensation of massage-like stroking resulting from social grooming, which is an important affiliative social behavior in the rodent. Blocking the sensation of social grooming in morphine-treated mice housed with drug-naive mice (i.e. morphine cage mates) significantly increased the display of jumping behavior in morphine-withdrawn animals. Activating the sensation of social grooming in morphine-treated animals housed solely with other morphine-treated animals (i.e. morphine only) did not significantly alter the display of jumping behavior in morphine-withdrawn animals. Repetitive jumping behaviors have been shown to correlate with morphine dependence. Thus, this study showed a role of social grooming in the protective effect of being housed with drug-naive mice on the development of morphine dependence. It further confirms a role of social support in the development of substance use problems.

Cervical cancer in southern Malawi: A prospective analysis of presentation, management, and outcomes.

BACKGROUND: Malawi has the highest age standardised rate of cervical cancer in the world. This study describes the presentation, management and short-term outcomes of patients with newly diagnosed cervical cancer at Queen Elizabeth Central Hospital (QECH), in Southern Malawi. METHODS: All patients with a new diagnosis of cervical cancer presenting to QECH between 1st January-1st July 2015 had demographic data, referral pathway, stage, histology and management prospectively recorded at presentation, and at two months after initial presentation. RESULTS: 310 women presented with cervical cancer to QECH and 300 were included (mean age 44.9 years; HIV 47%), representing 8% of the estimated annual number of new presentations in Malawi. Mean age of patients with HIV was 6.9 years younger compared to those without HIV (p<0.05). 132 (44%) patients had stage 1 cervical cancer and 168 (56%) presented with more advanced disease (stage II-IV). There was a mean delay of 23.1 weeks between onset of symptoms and being seen by a clinician and a further 19 weeks before attending QECH. Most common management plans at initial consultation were: same day biopsy (n=112, 37.3%);, booking for curative surgery (n=76, 25.3%);, and referral to palliative care (n=93, 31%). At 2 months, 64 (57%) biopsies were reported, 31 (40.8%) operations were completed and 27 (29%) patients had attended the palliative clinic. CONCLUSIONS: Patients presenting with cervical cancer to QECH were young, with a high prevalence of HIV, and late stage disease. The lack of pathological and surgical capacity and the absence of radiotherapy severely limited the possibility of curative treatment. Access to quality palliative care remains an important component of management in low resource settings. Improving awareness of cervical cancer in the community, and better recognition and management within the health service, are important in reducing the cancer burden for women in Malawi.

Opioid addiction: Who are your real friends?

Opioid addiction is a chronic and relapsing mental health disorder. However, only some individuals exposed to opioids, either recreationally or during the course of pain management, will develop addiction. The reasons why some individuals develop addiction and some are spared are not fully understood. Studies indicate that it is likely a combination of genetic predispositions and environmental conditions. Given the role of environmental factors in human addiction, this review examines the role of social environments and social interactions in the development of opioid addictive-like behaviors in rodent studies. To date, three major behavioral approaches have been used in these studies, namely social isolation, environmental enrichment, and social housing with a variety of cage-mates that differ in their drug administration conditions. This review highlights the importance of an individual's social network in influencing the outcomes of drug abuse and the need to further elucidate the molecular mechanisms underlying these effects. Better understanding is likely to contribute to the development of novel and more effective treatments for addiction disorders.

Hydrocodone is More Effective than Morphine or Oxycodone in Suppressing the Development of Burn-Induced Mechanical Allodynia.

BACKGROUND: Pain is the most frequent complaint of burn-injured patients. Opioids are commonly used in the course of treatment. However, there is a lack of rodent studies that examine the differential effects of various opioids on burn pain. OBJECTIVE: This study compared the ability of morphine, oxycodone, and hydrocodone to suppress the development of burn-induced mechanical allodynia and reduce pain sensitivity. METHODS: Mice were examined for their baseline pain sensitivity thresholds using the von Frey Filaments test. Then, they were subjected to burn or sham injury and treated orally with morphine, oxycodone, hydrocodone (20 or 40 mg/kg), or saline twice daily throughout the study. They were retested on days 4, 7, 11, 14, 21, and 28 postburn. RESULTS: In the sham animals, morphine produced significant opioid-induced hyperalgesia (OIH). Development of OIH was minimal for hydrocodone and was not observed for oxycodone. Secondary mechanical allodynia was observed beginning four days after the burn injury and intensified with time. All opioids produced comparable antinociceptive effects. Hydrocodone was effective in suppressing the development of burn-induced mechanical allodynia and fully treated the burn-induced increase in pain sensitivity. In contrast, morphine and oxycodone had only minimal effects on the development of burn-induced mechanical allodynia and only partially treated the burn-induced increase in pain sensitivity. CONCLUSIONS: This study demonstrated that hydrocodone is effective in suppressing the development of burn-induced mechanical allodynia, while both morphine and oxycodone had minimal effects. These findings underscore the need for additional studies on the differences among various opioids using clinically relevant pain models.

Hydrocodone, but Neither Morphine nor Oxycodone, Is Effective in Suppressing Burn-Induced Mechanical Allodynia in the Uninjured Foot Contralateral to the Burn.

Opioids are commonly used to treat severe, burn-induced pain. However, there is a lack of rodent studies that examine the differential effects of various opioids on burn pain. We recently demonstrated that hydrocodone was superior to other opioids in suppressing the development of burn-induced mechanical allodynia in the burned limb. This study monitored the development of mechanical allodynia and compared the abilities of morphine, oxycodone, and hydrocodone to reduce burn-induced mechanical allodynia in the limb contralateral to the burn. Mice were examined for their baseline pain sensitivity thresholds using the von Frey filaments test. Then, they were subjected to burn or sham injury and treated orally with morphine, oxycodone, hydrocodone (20 or 40 mg/kg), or saline twice daily throughout the study. They were retested on days 4, 7, 11, 14, 21, and 28 postburn. Hyperalgesia was developed in the contralateral, uninjured foot beginning 21 days after the burn injury. Hydrocodone was effective in suppressing the development of burn-induced mechanical allodynia. In contrast, morphine and oxycodone had only minimal effects on the development of burn-induced mechanical allodynia. The abnormal pain sensitivities that develop as a result of burn injuries are very difficult to treat and remain a significant public health problem. More rodent studies are required to improve our understanding of the differences among the currently available opioid analgesics in order to optimize the care provided to burn victims as well as those suffering from other pain modalities.

Burn injury decreases the antinociceptive effects of opioids.

Burn victim patients are frequently prescribed opioids at doses that are significantly higher than standard analgesic dosing guidelines, and, even despite an escalation in opioid dosing, many continue to experience pain. Thus, the aim of this study was to determine the effect of burn injury on opioid antinociception. Mice were examined for their baseline pain sensitivity thresholds using the von Frey filaments test. Then, they were subjected to burn or sham injury to the dorsal surface of the hindpaw and treated orally with morphine, oxycodone, hydrocodone (20 or 40 mg/kg), or saline twice daily throughout the study. They were retested on days 4, 7, 11, 14, 21, and 28 following the burn injury. The antinociceptive effects of the various drugs were analyzed by computing the daily difference between pain sensitivity threshold scores (in g) before and after treatment. This study showed that burn injury decreases opioid antinociception potency. A marked reduction was observed in the antinociceptive effectiveness of all opioids, and for both doses, in the burn-injured versus the sham animals. These results suggest that burn trauma limits the ability of opioids to be effective in reducing pain.