Pain-suppressed consumption of highly palatable liquid in rats.

This study determined whether consumption of a highly palatable liquid is a reliable measure of inflammatory pain and antinociception in male and female rats. After a 10-day acquisition period, the impact of intraplantar oil vs. complete Freund adjuvant (CFA) on consumption of vanilla-flavored Ensure was assessed, with a sipper tube height 12 or 19 cm above the floor.

Pain mechanisms in the transgender individual: a review.

Specific Aim: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research.

Methods: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research.

Impact of continuous testosterone exposure on reproductive physiology, activity, and pain-related behavior in young adult female rats.

Testosterone may reduce pain in cisgender women and transgender men. Rodents can provide a useful model for investigating physiological effects of hormone therapy. To this end, continuous-release testosterone or blank (placebo) capsules were implanted s.

Vaporized cannabis extract-induced antinociception in male vs female rats with persistent inflammatory pain.

Although preclinical studies generally report robust antinociceptive effects of cannabinoids in rodent persistent pain models, randomized controlled trials in chronic pain patients report limited pain relief from cannabis/cannabinoids. Differences between animal and human studies that may contribute to these discrepant findings include route of cannabis/cannabinoid administration, type of cannabis/cannabinoid, and how pain is measured. To address these factors, rats with complete Freund adjuvant (CFA)-induced hind paw inflammation were exposed acutely or repeatedly to vaporized cannabis extract that was either tetrahydrocannabinol (THC) or cannabidiol (CBD)dominant.

Burrowing as an index of inflammatory pain in male vs. female rats.

The study objective was to determine whether burrowing behavior is useful as a functional index of pain in both male and female rats, and whether a 'no-training' protocol can be used to increase testing efficiency. Adult Sprague-Dawley rats were injected in one or both hindpaws with oil vehicle or complete Freund's adjuvant (CFA); starting the next day, the amount of gravel each rat burrowed out of a tube in 1 h was measured daily for ≤7 days. Without preliminary training on the burrowing procedure, CFA reliably suppressed burrowing for 2-3 days compared to controls, in both sexes.

Cannabidiol and Delta-9-Tetrahydrocannabinol Interactions in Male and Female Rats With Persistent Inflammatory Pain.

Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), 2 of the primary constituents of cannabis, are used by some individuals to self-treat chronic pain. It is unclear whether the pain-relieving effects of CBD alone and in combination with THC are consistent across genders and among types of pain. The present study compared the effects of CBD and THC given alone and in combination in male and female rats with Complete Freund's adjuvant-induced inflammatory pain.

Adolescent THC exposure: effects on pain-related, exploratory, and consummatory behaviors in adult male vs. female rats.

Rationale: Adolescent cannabinoid exposure has been shown to alter cognitive, reward-related, and motor behaviors as well as mesocorticolimbic dopamine (DA) function in adult animals. Pain is also influenced by mesocorticolimbic DA function, but it is not known whether pain or cannabinoid analgesia in adults is altered by early exposure to cannabinoids.

Objective: To determine whether adolescent Δ-tetrahydrocannabinol (THC) exposure alters pain-related behaviors before and after induction of persistent inflammatory pain, and whether it influences antinociceptive of THC, in adult rats, and to compare the impact of adolescent THC exposure on pain to its effects on known DA-dependent behaviors such as exploration and consumption of a sweet solution.

No antinociceptive synergy between morphine and delta-9-tetrahydrocannabinol in male and female rats with persistent inflammatory pain.

Studies have demonstrated antinociceptive synergy between morphine and delta-9-tetrahydrocannabinol (THC) in animals, but whether such synergy occurs against all types of pain and in humans is unclear. Because a majority of chronic pain patients are women, and sex differences in morphine and THC potencies have been observed in rodents, the present study examined sex-specific effects of morphine and THC given alone and in combination, in rats with persistent inflammatory pain. On day 1, baseline mechanical and thermal response thresholds, hindpaw weight-bearing, locomotor activity, and hindpaw thickness were determined.

A Large-Scale Naturalistic Examination of the Acute Effects of Cannabis on Pain.

Cannabis use for pain relief is commonly reported, yet laboratory studies and clinical trials suggest that cannabinoids are weak analgesics, and it is unclear whether perceived reductions in pain from before to after cannabis use relate to factors such as dose, method of administration, phytocannabinoid content, or the age or gender of the user. We determined whether inhalation of cannabis decreased self-reported pain ratings as well as whether user gender, age, time, method of administration, tetrahydrocannabinol (THC)/cannabidiol (CBD) content, or dose of cannabis contribute to changes in these ratings. We also examined whether tolerance may develop to the analgesic effects of cannabis over time.

Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB receptor agonist ABK5.

Cannabinoid receptors are a potential target for anti-inflammatory and pain therapeutics. There are two subtypes, CB and CB, and Δ-tetrahydrocannabinol activates both of them, providing an analgesic effect but also psychoactive side effects. The psychoactive side effects are considered to be caused by activation of CB, but not CB.

Antinociception produced by nonsteroidal anti-inflammatory drugs in female vs male rats.

The primary aim of this study was to examine sex differences in acute antinociceptive and anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in rats. Complete Freund's adjuvant (CFA) was administered to adult Sprague-Dawley rats to induce pain and inflammation in one hindpaw; 2.5 h later, vehicle or a single dose of the NSAIDs ibuprofen (1.

Antinociceptive and Immune Effects of Delta-9-Tetrahydrocannabinol or Cannabidiol in Male Versus Female Rats with Persistent Inflammatory Pain.

Chronic pain is the most common reason reported for using medical cannabis. The goal of this research was to determine whether the two primary phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective treatments for persistent inflammatory pain. In experiment 1, inflammation was induced by intraplantar injection of Complete Freund's adjuvant (CFA).

Short- and Long-Term Effects of Cannabis on Headache and Migraine.

Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse. We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs flower), delta-9-tetrahydrocannabinol, cannabidiol, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects.

Effect of hyperbaric oxygen on chemotherapy-induced neuropathy in male and female rats.

Chemotherapeutic agents can cause peripheral neuropathy, a deleterious side effect of cancer treatment. Hyperbaric oxygen (HBO2) treatment has shown great potential for decreasing pain in numerous clinical pain conditions and in preclinical studies. This study was designed to test whether HBO2 might also be useful for treating chemotherapy-induced peripheral neuropathy.

Age-related differences in Δ⁹-tetrahydrocannabinol-induced antinociception in female and male rats.

Given the use of cannabis as an analgesic by a broadening age range of patients, the aim of this study was to determine whether the antinociceptive effects of Δ9-tetrahydrocannabinol (THC) differ by age. The antinociceptive potency and efficacy of THC (1.0-18 mg/kg ip) was compared in male and female rats aged postnatal day 35-40 (adolescent), 60-70 (young adult), and 291-325 (middle-aged adult), using warm water tail withdrawal and paw pressure tests.

Sex, THC, and hormones: Effects on density and sensitivity of CB cannabinoid receptors in rats.

Background: The recent NIH mandate to consider sex as a biological variable in preclinical research has focused attention on delineation of sex differences in behavior. To investigate mechanisms underlying sex differences in Δ-tetrahydrocannabinol (THC) effects, we examined the effects of sex and gonadal hormones on CB receptors in cerebellum, hippocampus, prefrontal cortex, and striatum.

Methods: Adult Sprague-Dawley rats underwent gonadectomy (GDX) or sham-GDX.

Cannabidiol modulation of antinociceptive tolerance to Δ-tetrahydrocannabinol.

Rationale: Humans typically self-administer cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) together repeatedly (as in cannabis, cannabis extract, or Sativex®) to relieve pain. It has been suggested that one benefit of the drug combination may be decreased tolerance development.

Objective: The present study compared the development of tolerance to the antinociceptive effects of THC given alone versus combined with CBD, in rats.

The Lateral Habenula Directs Coping Styles Under Conditions of Stress via Recruitment of the Endocannabinoid System.

Background: The ability to effectively cope with stress is a critical determinant of disease susceptibility. The lateral habenula (LHb) and the endocannabinoid (ECB) system have independently been shown to be involved in the selection of stress coping strategies, yet the role of ECB signaling in the LHb remains unknown.

Methods: Using a battery of complementary techniques in rats, we examined the localization of type-1 cannabinoid receptors (CBRs) and assessed the behavioral and neuroendocrine effects of intra-LHb CBR manipulations.

Anti-migraine effect of ∆-tetrahydrocannabinol in the female rat.

Current anti-migraine treatments have limited efficacy and many side effects. Although anecdotal evidence suggests that marijuana is useful for migraine, this hypothesis has not been tested in a controlled experiment. Thus, the present study tested whether administration of ∆-tetrahydrocannabinol (THC) produces anti-migraine effects in the female rat.

Antinociceptive effects of JWH015 in female and male rats.

Despite greater chronic pain prevalence in females compared with males, and the analgesic potential of cannabinoid receptor type 2 (CB2) agonists, CB2 agonists have rarely been tested in females. The aim of the present study was to compare the antinociceptive effects of a CB2-preferring agonist, (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), in female and male rats against acute pain and persistent inflammatory pain. JWH015 (5-20 mg/kg, intraperitoneally) produced dose-dependent and time-dependent increases in latency to respond on the tail withdrawal and paw pressure tests that did not differ statistically between the sexes.

Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective.

Recent policy changes have led to significant increases in the use of cannabis for both medical and recreational purposes. Although men are more likely to endorse past month cannabis use and are more frequently diagnosed with Cannabis Use Disorder relative to women, a growing proportion of medical cannabis users are reported to be women. The increased popularity of cannabis for medical purposes and the narrowing gap in prevalence of use between men and women raises questions regarding sex-dependent effects related to therapeutic efficacy and negative health effects of cannabis and cannabinoids.

Cannabidiol-Δ-tetrahydrocannabinol interactions on acute pain and locomotor activity.

Background: Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Δ-tetrahydrocannabinol's (THC) effects. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism.

Methods: In Experiment 1, CBD (0, 10 or 30mg/kg) was administered 15min before THC (0, 1.

Comparison of the discriminative stimulus and response rate effects of -tetrahydrocannabinol and synthetic cannabinoids in female and male rats.

Background: Women report greater sensitivity to the subjective effects of Δ-tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats.

Sex differences in alcohol consumption and alterations in nucleus accumbens endocannabinoid mRNA in alcohol-dependent rats.

Chronic intermittent alcohol (CIA) exposure produces altered motivational states characterized by anxiety and escalated alcohol consumption during withdrawal. The endocannabinoid (ECB) system contributes to these symptoms, and sex differences in alcohol dependence, as well as bidirectional interactions between ECBs and gonadal hormones have been documented. Thus, we evaluated sex differences in alcohol consumption, anxiety-like behavior, and ECB mRNA expression in the nucleus accumbens (NAc) of alcohol-dependent rats during acute withdrawal.

The impact of gonadal hormones on cannabinoid dependence.

Cannabis is the most widely used illicit substance in the United States. Women report greater positive subjective effects of cannabis, and greater cannabis withdrawal compared to men. Female rodents are more sensitive than males to some acute effects of Δ⁹-tetrahydrocannabinol (THC), and females also develop greater tolerance to THC in some assays.