Ketamine: Basic Science Evidence for Its Efficacy

Chemotherapy-Induced Pain

In two separate studies, systemic ketamine injections reduced pain behaviors in mechanical allodynia and thermal hyperalgesia rats. Interestingly, a higher dose of ketamine was required to significantly reduce pain thresholds in male rats compared to female rats.

Neuropathic Pain Caused by Nerve Injury

Animal models for nerve injury-induced neuropathic symptoms include spinal nerve ligation, chronic constriction (CCI), sparing nerve injury (SNI), and constriction of the infraorbital nerve.

However, high doses (25, 50 mg/kg) produced adverse effects, including motor impairment. Additionally, repeated systemic administration or systemic infusion of ketamine reduced mechanical pain in SNL rats at doses of 3, 10, or 40 mg/kg/day. In the SNL rat model, intrathecal injections of ketamine at doses of 10, 30, 100 mg/kg reduced mechanical allodynia, indicating that the spinal cord was the major site of ketamine’s action.

The SNI model showed that repeated systemic injections or injections of ketamine for a total of 5 days at a dose of 3 mg/kg/h or 9 mg/kg/day reduced mechanical and cold pain for several weeks. A single systemic injection at 10 mg/kg did not have analgesic effects.

In the CCI model, systemic administration of ketamine at doses of 30, 40, and 50 mg/kg reduced heat hyperalgesia as well as mechanical allodynia over several hours. The ED25 of ketamine was 31.8 mg/kg when administered subcutaneously. Diabetic Neuropathic Pain

Chronic diabetes often manifests as neuropathic symptoms and can be modeled in mice by high-dose injections of streptozotocin, which selectively kills beta cells via DNA alkalization.

In two studies of streptozotocin-induced diabetic neuropathy, systemic infusion of ketamine at 20 mg/kg/day for 5 days reduced heat and mechanical hyperalgesia for several weeks following treatment. In another study, mice treated with ketamine showed some opioid-sparing properties for up to six weeks, as well as increased sensitivity to the acute nociceptive effect of morphine.

Other Neuropathic Pain

There are many more animal models of neuropathic conditions that can be used to test the effectiveness of ketamine. Ketamine was shown to reduce pain in various models, including arthritis, distal fractures and castings, ischemia-reperfusion, herpetic pain, and ischemia.

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