Topical and Peripheral Ketamine as an Analgesic

Abstract

Ketamine, in subanesthetic doses, produces systemic analgesia in chronic pain settings, an action largely attributed to block of N-methyl-D-aspartate receptors in the spinal cord and inhibition of central sensitization processes. N-methyl-D-aspartate receptors also are located peripherally on sensory afferent nerve endings, and this provided the initial impetus for exploring peripheral applications of ketamine. Ketamine also produces several other pharmacological actions (block of ion channels and receptors, modulation of transporters, anti-inflammatory effects), and while these may require higher concentrations, after topical (e.g., as gels, creams) and peripheral application (e.g., localized injections), local tissue concentrations are higher than those after systemic administration and can engage lower affinity mechanisms. Peripheral administration of ketamine by localized injection produced some alterations in sensory thresholds in experimental trials in volunteers and in complex regional pain syndrome subjects in experimental settings, but many variables were unaltered. There are several case reports of analgesia after topical application of ketamine given alone in neuropathic pain, but controlled trials have not confirmed such effects. A combination of topical ketamine with several other agents produced pain relief in case, and case series, reports with response rates of 40% to 75% in retrospective analyses. In controlled trials of neuropathic pain with topical ketamine combinations, there were improvements in some outcomes, but optimal dosing and drug combinations were not clear. Given orally (as a gargle, throat swab, localized peritonsillar injections), ketamine produced significant oral/throat analgesia in controlled trials in postoperative settings. Topical analgesics are likely more effective in particular conditions (patient factors, disease factors), and future trials of topical ketamine should include a consideration of factors that could predispose to favorable outcomes.

Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy

“…Therefore, ketamine may reduce the development of chronic postoperative pain via NMDA receptor blockade, which reduces wind-up and central sensitization. [11] …”

“…[11] It also acts as a noncompetitive N -methyl- d -aspartate (NMDA) receptor antagonist, which reduces acute postoperative pain and prevents the development of chronic postoperative pain. [11] It may be administered perioperatively for postoperative pain as an adjuvant to systemic opioids, with fewer adverse effects [12] ; however, the effects of perioperative ketamine infusion on postoperative pain following BABA robotic or endoscopic thyroidectomy have not been investigated. We hypothesized that low doses of ketamine infused during surgery would reduce postoperative pain.…”

Chemogenomics knowledgebase and systems pharmacology for hallucinogen target identification—Salvinorin A as a case study

“…Moreover, various studies pointed out great anti-depressive effect of ketamine (13). Ketamine can also act as an analgesic by blocking N-methyl-D-aspartate receptors (14). New applications of ketamine emerge nowadays, such as the less established treatment for post-traumatic epilepsy, and anesthesia in the emergency department and operating theater setting (14, 15).…”

Comparison of the Effects of Topical Ketamine and Tramadol on Postoperative Pain After Mandibular Molar Extraction

“…Other studies used ketamine topically after tonsillectomy; the treatment produced an analgesic effect and decreased the need for rescue medication. [14][15][16] Satilmiş et al 12 investigated the efficacy of adding ketamine to local anesthetic agents to increase the duration of regional anesthesia and postoperative analgesia during surgical extraction of third molars. They concluded that the combination of a local anesthetic and sub-anesthetic doses of ketamine can produce good local anesthesia.…”