This and other research indicate that cannabinoid system and TRPV1 may play an important role in the analgesic effect of paracetamol. Pharmacokinetics
After being taken by mouth, paracetamol is rapidly absorbed from the small intestine, while absorption from the stomach is negligible. Thus, the rate of absorption depends on stomach emptying. Food slows the stomach emptying and absorption, but the total amount absorbed stays the same. In the same subjects, the peak plasma concentration of paracetamol was reached after 20 minutes when fasting versus 90 minutes when fed. High carbohydrate, but not high protein or high fat, food decreases paracetamol peak plasma concentration by four times. Even in the fasting state, the rate of absorption of paracetamol is variable and depends on the formulation, with maximum plasma concentration being reached after 20 minutes to 1.5 hours.Paracetamols bioavailability is dose-dependent: it increases from 63% for 500 mg dose to 89% for 1000 mg dose. Its plasma terminal elimination half-life is 1.9–2.5 hours, and volume of distribution is roughly 50 L. Protein binding is negligible, except under the conditions of overdose, when it may reach 15–21%. The concentration in serum after a typical dose of paracetamol usually peaks below 30 μg/mL (200 μmol/L). After 4 hours, the concentration is usually less than 10 μg/mL (66 μmol/L). Paracetamol is metabolized primarily in the liver, mainly by glucuronidation and sulfation, and the products are then eliminated in the urine (see the Scheme on the right). Only 2–5% of the drug are excreted unchanged in the urine.
Similarly, European algorithm ESCEO for the treatment of knee osteoarthritis recommends limiting the of use paracetamol to short-term rescue analgesia only.Paracetamol is ineffective for acute low back pain. No randomized  clinical trials evaluated its use for chronic or radicular back pain, and the evidence in favor of paracetamol is lacking. Headaches
Paracetamol is effective for acute migraine: 39% of people experience pain relief at one hour compared with 20% in the control group. The aspirin/paracetamol/caffeine combination also "has strong evidence of effectiveness and can be used as a first-line treatment for migraine." The German, Austrian, and Swiss headache societies and the German Society of Neurology recommend the combination as a "highlighted" one for self-medication of migraine, and paracetamol alone as a first choice.Paracetamol on its own only slightly alleviates episodic tension headache in those who have them frequently. However, the aspirin/paracetamol/caffeine combination is superior to both paracetamol alone and placebo and offers meaningful relief of tension headache: 2 hours after administering the medication, 29% of those who took the combination were pain free as compared with 21% on paracetamol and 18% on placebo. The German, Austrian, and Swiss headache societies and the German Society of Neurology recommend this combination as a "highlighted" one for self-medication of tension headache, with paracetamol/caffeine combination being a "remedy of first choice", and paracetamol a "remedy of second choice". Dental and other post-surgical pain
Pain after a dental surgery provides a reliable model for the action of analgesics on other kinds of acute pain.