Chronic THC vapor inhalation rescues hyperalgesia in rats with chronic inflammation and produces sex-specific alterations in midbrain neuronal activity
Bibliographic record
Abstract
Abstract In an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic THC vapor inhalation effects on thermal nociception and mechanical sensitivity, as well as midbrain (i.e., ventrolateral periaqueductal gray [vlPAG]) neuronal function, in adult male and female Wistar rats with chronic inflammatory pain (CFA treatment). We report that chronic THC vapor inhalation rescues both thermal hyperalgesia and mechanical hypersensitivity in males treated with CFA, but only thermal hyperalgesia in CFA females. Most of the anti-hyperalgesic effects of chronic THC vapor were still observable 24 hours after cessation of the last THC exposure. We also report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically in neurons that respond to current input with a “delayed” firing phenotype. Treatment with CFA led to increased firing rate and increased sIPSC amplitude in vlPAG neurons of female rats, and chronic THC vapor rescued sIPSC amplitudes to control levels – these effects were specific to vlPAG neurons categorized as having an “onset” firing phenotype. Ongoing work is exploring sex-specific mechanisms (e.g., CB1 receptor) of THC vapor rescue effects in the vlPAG of rats treated with CFA, and further exploring the vlPAG cell types impacted by CFA treatment and chronic THC vapor inhalation. Significance Statement Many adults in the U.S. with pain self-medicate with THC and cannabis, and many humans use e-cigarette type devices filled with cannabis extracts to self-administer THC and other constituents of the marijuana plant. Until recently, most rodent studies of THC effects on brain and behavior have used injection procedures and male rats. Here, we tested the effect of chronic THC vapor inhalation on pain-related behaviors and midbrain neural circuit function in adult male and female Wistar rats. As predicted, chronic THC vapor inhalation rescued chronic inflammatory pain effects on behavior and midbrain neuronal function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".