NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride

Abstract

Ten patients (4 female, 6 male) aged 34-67 years suffering from peripheral neuropathic pain participated in a double-blind placebo-controlled study where ketamine or magnesium chloride were administered by a 10 min bolus infusion (ketamine: 0.84 mumol/kg = 0.2 mg/kg, magnesium: 0.16 mmol/kg) followed by a continuous infusion (ketamine: 1.3 mumol/kg/h = 0.3 mg/kg/h, magnesium: 0.16 mmol/kg/h). Ongoing pain determined by VAS score, area of touch-evoked allodynia, detection and pain thresholds to mechanical and thermal stimuli were measured before and during drug infusion. Ketamine produced a significant reduction of spontaneous pain (57%) and of the area of allodynia (33%). Magnesium chloride reduced pain (29%) and area of allodynia (18%) insignificantly. Following ketamine there was a significant correlation between the reduction in ongoing pain and reduction in area of touch-evoked allodynia. Detection and pain thresholds to mechanical and thermal stimuli were not significantly changed by the drugs. These findings suggest that both ongoing pain and touch-evoked pain (allodynia) in neuropathic pain are inter-related phenomena, which may be mediated by the same mechanism and involving a N-methyl-D-aspartate receptor.

Zinc modulates primary afferent fiber-evoked responses of ventral roots in neonatal rat spinal cord in vitro

“…The long-term potentiation evoked by tetanic electrical stimulation is prevented by NMDA receptor antagonists in the rat spinal cord (Randi•, et al, 1993;Liu and Sandkühler, 1995). Ketamine is clinically used as an anesthetic agent and alleviates hyperalgesia and allodynia in the rat (Qian et al, 1996;Chaplan et al, 1997) and human (Felsby et al, 1995;Ilkjaer, et al, 1996). The fact that ketamine inhibits the excitatory effect of Zn 2+ suggests that Zn 2+ enhances nociceptive transmission in the spinal cord of the neonatal rat.…”

Ketamine used as an acesodyne in human breast cancer therapy causes an undesirable side effect, upregulating anti-apoptosis protein Bcl-2 expression

“…For early experience, ketamine can produce analgesia that sometimes well outlasts its anesthetic effects. The mechanisms of the analgesic effects of ketamine are debated (Felsby et al, 1996;Ilkjaer Control siRNA means negative siRNA control. All data are reported as means ± SD for 3 independent experiments.…”

“…The utility of ketamine as an anesthetic has been hampered by its troublesome psychomimetic effects. Previous studies have shown that analgesia can be produced with subhypnotic doses of intravenous ketamine with a lower frequency of psychomimetic reactions to provide relief for patients experiencing intractable cancer pain (Backonja et al, 1994;Felsby et al, 1996;Ilkjaer et al, 1996;Warncke et al, 1997;Bell et al, 2003;Slatkin and Rhiner, 2003).…”

The Use of Ketamine in Neuropathic Pain

“…There are at least 9 randomized, double-blind trials demonstrating the efficacy of ketamine in NP [66][67][68][69][70][71][72][73][74][75]. In patients with post-nerve injury NP, ketamine administered IV has shown significant reduction in pain and allodynia as compared to placebo [66-70, 73, 74] as well as compared to morphine [73].…”