Background: There is growing evidence suggesting that hypothalamic galanin (GAL), which is known to stimulate intake of a fat-rich diet, has a role in promoting the consumption of ethanol. The present study further examined this possibility in GAL knockout (GALKO) mice.Methods: Two groups of female and male GALKO mice, compared to wild-type (WT) controls, were trained to voluntarily drink increasing concentrations of ethanol, while maintained on lab chow and water. They were examined in terms of their daily ethanol intake and preference, acute consumption of a high-fat diet, preference for flavored solutions, and expression of different peptides shown to stimulate ethanol intake.Results: In the GALKO mice compared to WT, the results revealed: (i) a 35 to 45% decrease in ethanol intake and preference, which was evident only at the highest (15%) ethanol concentration, was stronger in female than in male mice, and was seen with comparisons to littermate as well as nonlittermate WT mice; (ii) a 48% decrease in acute intake of a fat-rich diet, again stronger in female than male mice; (iii) no difference in consumption of sucrose or quinine solutions in preference tests; (iv) a total loss of GAL mRNA in the hypothalamic paraventricular nucleus (PVN) of female and male mice; and (v) a gender-specific change in mRNA levels of peptides in the perifornical lateral hypothalamus (PFLH), orexin and melanin-concentrating hormone, which are known to stimulate ethanol and food intake and were markedly decreased in females while increased in males.Conclusions: These results provide strong support for a physiological role of PVN GAL in stimulating the consumption of ethanol, as well as a fat-rich diet. Ablation of the GAL gene produced a behavioral phenotype, particularly in females, which may reflect the functional relationship of galanin to ovarian steroids. It also altered the peptides in the PFLH, with their reduced expression contributing to the larger behavioral effects observed in females and their increased expression attenuating these effects in males.
Increasing interest in MMJ for chronic pain underscores a need for primary care and pain physicians to better understand the indications and evidence for its use free from cultural bias. Given a lack of full conclusive clinical utility, continued research is needed to better understand how to best utilize MMJ therapy for the treatment of chronic pain. Policy initiatives, such as enumerated indications, should follow medical science in order to prevent another abused substance epidemic.
Migraine can impact every aspect of a person's functioning. Psychological comorbidities, cognitive constructs, and behavioral responses to pain greatly impact the perception of migraine pain, treatment efficacy and outcome, and overall quality of life and functioning. Current considerations for migraine treatment emphasize the utility of the biopsychosocial model in understanding and treating migraine, noting both the importance of addressing psychological factors such as cognitive beliefs as well as psychiatric comorbidities. The guidelines for migraine treatment implicate opioid therapy as a second or third tier treatment. Guidelines and recommendations for the safe use of opioid medications among patients with chronic pain emphasize the importance of screening prior to prescribing opioid medications. Chronic opioid therapy has been shown to further levels of disability, decrease quality of life, and correlate to psychiatric comorbidities, concerns that are already present in migraine patients. While opioid treatment provides an alternative for persons with contraindications for alternative migraine treatments, it is critical that opioids be used sparingly and exclusively in conjunction with comprehensive assessment and integration of psychological treatment.
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