The Influence of Adenosine, Ketamine, and Morphine on Experimentally Induced Ischemic Pain in Healthy Volunteers

Abstract

Adenosine, intrathecally administered, produces antinociception in experimental studies on animals. The effect of intravenous (i.v.) adenosine on experimentally induced pain in humans has not been studied. The present single-blind, randomized, placebo-controlled study was conducted in nine healthy volunteers. The pain-reducing effects of adenosine (70 micrograms.kg-1.min-1 i.v.), morphine (0.1 mg/kg i.v.), ketamine (0.1 mg/kg i.v.), adenosine + morphine, and adenosine + ketamine were compared to each other and to placebo in random order. Ischemic pain was induced by the submaximum effort tourniquet technique. Pain was assessed using the visual analog scale (VAS, 0-100 mm). The sums of pain scores (SPS) were compared and found significantly 30%-40% lower for adenosine as well as for the other compounds and combinations (P < 0.03), compared to placebo. The number of subjects who reached VAS 100 within 30 min was significantly lower (P < 0.03) when receiving adenosine + morphine (0/9) and adenosine + ketamine (2/9) than when receiving placebo (7/9). This may indicate an additive effect on pain reduction when adenosine is given in combination with morphine or ketamine. In conclusion, the results indicate that i.v. adenosine, as well as morphine and ketamine, can reduce experimentally induced ischemic muscle pain in healthy volunteers.

Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

“…Muscle hyperalgesia. Hyperalgesia produced by eccentric muscle contraction was decreased by morphine (Smith et al, 1966;Segerdahl et al, 1994). In contrast, hyperalgesia after intramuscular injection of nerve growth factor was unaffected by fentanyl (Andresen et al, 2010).…”

“…response to electrical stimulations was decreased by morphine (Smith et al, 1966;Segerdahl et al, 1994;Plesan et al, 2000;Pud et al, 2006). Pain in response to hypertonic saline was sensitive to modulation from morphine when a high dose was administered (Schulte et al, 2003(Schulte et al, , 2006.…”

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

“…Ischaemic pain, cold pressor pain and pain to electrical stimulations were decreased by morphine [87,[89][90][91][92]. Pain to hypertonic saline was sensitive to modulation from morphine when a high dose was administered [48,53].…”

“…Despite the fact that experimental pain models only explore a limited and differential part of the cascade of processes involved in clinical pain some models predict how the analgesic will behave in the clinic [124]. An example of this is the model of ischaemic muscle pain.This model is thought to mimic clinical inflammatory musculoskeletal pain and for morphine there is consensus between the findings in the model and the clinical situation [91,92]. Another example, showing the limit of experimental pain, is the capsaicin model, thought to mimic neuropathic pain because the evoked hyperalgesia has features (allodynia) that is seen also in the clinic.…”

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

“…Ketamine that is a strong agonist for particularly the NMDA receptor works well in models that activate the NMDA receptor, including models with repeated stimulation or strong and long-lasting pain [30,51,52,66]. However, this compound also decreases more shortlasting pain, despite the questionable activation of the NMDA receptor in such models [30,52].…”