Abstract
Cannabinoids help in pain treatment through their action on CB1 and CB2 receptors. β-caryophyllene (BCP), an ancient remedy to treat pain, is a sesquiterpene found in large amounts in the essential oils of various spice and food plants such as oregano, cinnamon, and black pepper. It binds to the CB2 receptor, acting as a full agonist. Sex differences in the BCP-induced analgesic effect were studied by exposing male and female rats to a persistent/repeated painful stimulation. To simulate treatment of a repeated inflammatory condition, after the first formalin injection (FT1; 50 μl, 2.5%), rats received BCP per os for 7 days at two dosages: 5 and 10 mg/kg dissolved in olive oil (OIL). The control group was treated with OIL for 7 days. On day 8, the formalin test was repeated (FT2) with a lower formalin concentration (50 μl, 1%). During the first and second formalin tests, pain-induced responses (licking, flexing, and paw jerk) and spontaneous behaviors were recorded and analyzed. In the FT1 (before the beginning of treatment with BCP), females displayed higher pain responses than did males in terms of flexing duration during the first part of the test (I phase and interphase), while during the second part (II phase early and late) males showed higher levels than did females in licking duration. In the FT2, the pain responses generally decreased in the BCP groups in a dose-dependent manner (i.e., greater effect of BCP10), with a more pronounced reduction in males than in females; moreover, the pain responses remained high in the OIL groups and in the female BCP5 group. In conclusion, long-term intake of BCP appears to be able to decrease pain behaviors in a model of repeated inflammatory pain in both sexes, but to a greater degree in males.
Highlights
In Europe, the number of chronic pain patients is approaching 50% of the population, most of them suffering pain daily and at high intensity
We have repeatedly shown that opioids, and analgesics in general, can induce hypogonadism, a BCP Decreases Pain in Rats persistent and serious side effect (Ceccarelli et al, 2006; Aloisi et al, 2009; Pergolizzi et al, 2010)
To mimic an animal model of recurrent pain, i.e., a common form of chronic pain during which acute short- or long-lasting episodes affect the patient for hours or days after which the symptoms disappear until the painful events, we carried out two formalin tests separated by a 1-week period
Summary
In Europe, the number of chronic pain patients is approaching 50% of the population, most of them suffering pain daily and at high intensity. We have repeatedly shown that opioids, and analgesics in general, can induce hypogonadism, a BCP Decreases Pain in Rats persistent and serious side effect (Ceccarelli et al, 2006; Aloisi et al, 2009; Pergolizzi et al, 2010). This condition impairs the nervous system (depression) as well as muscle tone (asthenia and fatigue), leading to further chronic pain (De Maddalena et al, 2012). Increased attention has been given to other plant-based compounds with less severe consequences for the patient’s body
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