Impact of Vitamin C on Pain Detection and Tolerance Threshold

Impact of Vitamin C on Pain Detection and Tolerance Threshold: a Double-blind Randomized Controlled Trial

Non-opioid treatments are increasingly sought after for managing acute pain. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (e.g., Advil, Motrin, Naproxen) combined with acetaminophen (e.g., Tylenol) have become an alternative for relieving acute pain. However, many patients cannot tolerate or have contraindications to NSAIDs and acetaminophen.

There is therefore an urgent need for studies evaluating the analgesic effects of vitamin C in the context of acute pain. Our study is conducted with healthy volunteer participants receiving either vitamin C or a placebo to assess the analgesic effect of vitamin C by comparing pain detection and tolerance thresholds.

Opioid-free treatments are increasingly sought for acute pain and NSAIDs have become an alternative to treat acute MSK pain and are often administered in addition to acetaminophen. However, NSAIDs can produce important adverse events and are contraindicated in many patients with comorbidities (e.g., heart disease, renal failure). Similarly, acetaminophen is contraindicated in patients with active liver disease or severe hepatic impairment.

Vitamin C has shown opioid sparing and anti-inflammatory effects mostly in postoperative contexts. Vitamin C has also demonstrated very low toxicity and rare contraindications at the dosage used in this study. Demonstrating that vitamin C increases pain detection and tolerance thresholds, thereby exhibiting an analgesic effect, could offer a valuable alternative or adjunct for patients who cannot tolerate or have contraindications to NSAIDs or acetaminophen, helping to reduce opioid use. With an aging population, the number of affected patients is expected to rise significantly.

The primary outcome is the pressure pain detection threshold (PPDT) measured with an algometer one to three hours after the last dose of the study drug (24 hours after the first dose of vitamin C or placebo).

Secondary outcomes are PPDT one to three hours after the first study drug dose, PPTT one to three hours after the initial dose and last dose of the study drug, and adverse events from the algometer or the vitamin C.

Inclusion Criteria:

1. Age ≥ 18 to 65 years old;
2. No acute or chronic pain;
3. No pain medication;
4. French or English-speaking

Exclusion Criteria:

1. Currently using vitamin C supplements;
2. Pain in the last week or active cancer;
3. Unavailable for follow-up;
4. Allergy to milk (lactose in the placebo), or vitamin C,
5. Treated with cyclosporine or warfarin (interaction with vitamin C);
6. Pre-existing oxalate nephropathy, liver cirrhosis or hemochromatosis;
7. Evidence of joint or overlying skin infection in the areas of testing.