Anaesthetic medication such as lidocaine and ketamine are sodium channel blockers and can be delivered by a number of routes. Ketamine is a non-competitive NMDA receptor antagonist that can be administered epidurally, intrathecally, and orally to treat neuropathic pain syndromes (Hocking & Cousins 2003).
| Author Year Country PEDro Score Research Design Total Sample Size | Methods | Outcome |
| Lidocaine | ||
| Finnerup et al. 2005 Denmark RCT PEDro=10 N=24 | Population: Type of pain=neuropathic. Treatment: Subjects were initially divided into two groups: those with and without evoked pain. In this cross-over design, each group then was subdivided (experimental vs. controls) with experimental group receiving 5 mg of lidocaine infused over 30 min; controls received placebo. Outcome Measures: McGill Pain Questionnaire (MPQ) | 1. In the total sample of patients, lidocaine reduced pain vs. placebo (p<0.01). 2. Assessing those with and without evoked pain, lidocaine still superior to placebo at reducing pain (p<0.01 and p<0.048, respectively). 3. More patients reported pain relief with at level and below-level pain while receiving lidocaine vs. placebo. |
| Kvarnstrom et al. 2004 Sweden RCT PEDro=10 N=10 | Population: Type of pain=neuropathic. Treatment: SCI patients were recruited for participation. Ketamine (0.4 mg/kg) vs. lidocaine (2.5 mg/kg) vs. saline placebo administered intravenously over 40 min. Outcome Measures: Visual Analogue Scale (VAS) | 1. VAS scores were significantly reduced in ketamine vs. the placebo group (p<0.01). 2. Comparing lidocaine and placebo group, no significant difference noted (p=0.60). 3. Pain relief was not linked to altered temperature thresholds or other changes in sensory function. |
| Attal et al. 2000 France RCT PEDro=10 N=16 | Population: Type of pain=neuropathic. Treatment: Patients participated, six with stroke and ten with SCI. Subjects given 5mg of lidocaine or saline over a 30 min period. Treatments given in separate sessions, 3 wk apart. Order of sessions was randomized. Outcome Measures: Visual Analogue Scale (VAS), McGill Pain Questionnaire (MPQ) | 1. Effects of lidocaine on pain were greater than effects of placebo, starting at end of injection, and lasting for up to 45 min post injection (p<0.05). 2. More people received pain relief with lidocaine than with placebo; however, relief waned by 60 min post injection. 3. Lidocaine reduced pain in 11 patients; and, in 6 of 12 patients, burning pain totally or partially relieved. 4. For those with brush-induced allodynia (n=8), lidocaine produced a reduction in intensity of allodynia 15 min post injection, and this lasted up to 30 min post injection. |
| Loubser & Donovan 1991 USA RCT PEDro=8 N=21 | Population: Age=18-58 yr; Gender: males=15, females=6; Level of injury: cervical, lumbar; Duration of chronic pain=>6 mo; Type of pain=nociceptive. Treatment: Subjects had a lumbar subarachnoid catheter inserted. Subjects recorded their pain intensity at baseline. This was followed by two separate injections (placebo and 5% lidocaine in dextrose). A decrease in pain was considered a positive response to the treatment. Outcome Measures: Pain. | 1. All 21 patients tolerated the injection (anaesthetics and placebo) well. 2. Negative placebo response was noted in 17 pts. Following lidocaine (n=13) patients showed a mean reduction in pain (p<0.01) for an average of 123.1± 95.3 min. 3. The decrease in pain reduction following lidocaine was significant (p<0.01) for the treatment group only. |
| Mexiletine | ||
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Chiou-Tan et al. 1996 USA RCT PEDro=8 Initial N=15; Final N=11
| Population: Mean age=44 yr; Gender: males=11, females=2; Severity of injury: AIS: A-E; Time since injury=7 yr.; neuropathic. Treatment: Following a 1 wk washout period subjects were given either 150 mg of mexiletine or placebo (150 mg 3x/day) followed by another 1 wk washout period then subjects placed in opposite group. Outcome Measures: McGill pain score. | 1. Visual analogue showed no significant differences for average pain levels over the past week and pain at time of test regardless of which medication (drug or placebo) subject was taking. 2. Results of the McGill Pain score also showed no significant differences between the groups. 3. No change in level of function for either group at any time of the study.
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| Ketamine | ||
| Amr 2010 Egypt RCT PEDro=6 N=40 | Population: Age=48.6yr; Gender: males=33, females=7; Type of pain=neuropathic. Treatment: Participants were randomly assigned to treatment or control group. Participants in the treatment received 80mg intravenous ketamine over a 5 hours period daily for 1 week and 300mg gabapentin 3 times daily. The placebo group received placebo infusion and 300 mg of gabapentin 3 times daily. Pain Scale: Visual Analogue Scale (VAS) | 1. Significant reduction in pain intensity was seen among individuals receiving ketamine infusion combined with gabapentin compared to those in the placebo group. The reduction remained significant up till 2 weeks post infusion (p<0.05).
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| Kvarnstrom et al. 2004 Sweden RCT PEDro=10 N=10 | Population: Type of pain=neuropathic. Treatment: SCI patients were recruited for participation. Ketamine (0.4 mg/kg) vs. lidocaine (2.5 mg/kg) vs. saline placebo administered intravenously over 40 min. Pain Scale: Visual Analogue Scale (VAS) | 1. VAS scores were significantly reduced in ketamine vs. the placebo group (p<0.01). 2. Comparing lidocaine and placebo group, no significant difference noted (p=0.60). 3. Pain relief was not linked to altered temperature thresholds or other changes in sensory function. |
| Eide et al. 1995 Norway RCT PEDro=7 N=9
| Population: Age=25-72 yr; Gender: males=8, females=1; Level of injury: cervical, thoracic; Severity of injury: AIS: A-D; Onset of pain: <6 mo post injury, Length of pain: 14-94 mo. Type of pain=neuropathic. Treatment: Ketamine hydrochloride, alfentanil or a placebo was given as combination of bolus and continuous intravenous infusions. The bolus dose was administered for 60 secs and the continuous intravenous infusion started simultaneously and was delivered by IVAC syringe pump. This lasted 17-21 min while the testing was performed. Outcome Measures: Visual Analogue Scale (VAS). | 1. Freidmann’s two-way analysis by ranks showed differences between the various treatments (p=0.005). 2. The effect of alfentanil and ketamine was also significant (p<0.01 and p<0.04 respectively). 3. No significant differences were noted between the actions of ketamine and alfentanil (Wilcoxon p=0.19). 4. Significant differences were noted between the treatment groups (p=0.008). It was also noted that allodynia was not more changed by ketamine than by alfentanil (Wilcoxon p=0.93). 5. Alfentanil reduced wind-up-like pain (p=0.014) compared to the placebo group. The effect of ketamine on wind-up-like pain was not significantly reduced (p=0.07). 6. A high correlation between the serum concentration of ketamine and the reduction of continuous pain (r=0.78, p<0.002) and the reduction of wind-up-like pain (r=0.83, p<0.002) was noted. |
| Study | Study Type | N | Intervention | Outcome |
| Finnerup et al. 2005 | RCT | 24 | Lidocaine | + |
| Attal et al. 2000 | RCT | 16 | Lidocaine | + |
| Kvarnstrom et al. 2004 | RCT | 10 | Lidocaine | – |
| Loubser & Donovan 1991 | RCT | 21 | Lidocaine | + |
| Chiou-Tan et al. 1996 | RCT | 15 | Mexiletine | _ |
| Kvarnstrom et al. 2004 | RCT | 10 | Ketamine | + |
| Eide et al. 1995 | RCT | 9 | Ketamine | + |
Lidocaine
Given the severity of post-SCI pain, treatments such as lumbar epidural and subarachnoid infusions or anaesthetics are sometimes utilized and there is some evidence for these treatments. Loubser and Donovan (1991) conducted an RCT of 21 patients who were provided two separate lumbar subarachnoid injections of placebo and 5% lidocaine in dextrose. Following the lidocaine injection (n=13) there was a significant mean reduction in pain (p<0.01) for an average of two hours despite the fact that eight patients showed no changes. However, this treatment provided short-term relief of pain only. The authors regarded the value of this treatment as more a diagnostic procedure than a therapeutic one.
Attal et al. (2000) reported on 15 patients who received lidocaine intravenously and experienced a greater reduction in pain than those who received placebo, with an effect lasting up to 45 minutes post injection, and a reduction in the intensity of brush-induced allodynia and mechanical hyperalgesia. In a RCT study by Finnerup et al. (2005) those patients who received lidocaine intravenously (n=24) in two treatment sessions six days apart reported significantly less pain than those who did not receive intravenous lidocaine.
Kvarnstrom et al. (2004) found no evidence for the effectiveness of intravenous lidocaine in reducing neuropathic pain when compared to placebo.
Mexilitine
Chiou-Tan et al. (1996) provided 15 SCI individuals with either oral mexiletine (an orally administered derivative of lidocaine) or placebo (150mg 3x daily) in a double-blind cross-over RCT. There was no appreciable improvement in pain severity, as measured either on a VAS or using the McGill Pain Questionnaire, within either group.
Ketamine
Three RCTs found ketamine was successful in reducing neuropathic pain post SCI (Amr 2010; Kvanrnstrom et al. 2004; Eide et al. 1995). Eide et al. (1995) in an RCT of intravenous ketamine hydrochloride (NMDA receptor antagonist), alfentanil (m-opioid receptor agonist) or placebo were provided as combination of bolus and continuous intravenous infusions. There was a significant benefit to ketamine or alfentanil vs. placebo for allodynia. Alfentanil reduced wind-up pain compared to placebo but not ketamine overall; however, there was a high correlation between the serum concentration of ketamine and the reduction in continuous pain and wind-up pain. The effects of ketamine and alfentanil were significant when compared to placebo.
There is level 1b evidence (from one randomized controlled trial; Loubser & Donovan 1991) that Lidocaine delivered through a subarachnoid lumbar catheter provides short-term relief of pain greater than placebo.
There is level 1a evidence (from two randomized controlled trials; Kvarnstrom et al. 2004; Eide et al. 1995) that intravenous Ketamine significantly reduces allodynia when compared to placebo.
There is level 1b evidence (from one randomized controlled trial; Chiou-Tan et al. 1996) that mexilitene (a derivative of lidocaine) does not improve SCI dysesthetic pain when compared to placebo.
Lidocaine through a subarachnoid lumbar catheter and intravenous Ketamine improve post-SCI neuropathic pain short term.
Mexilitene does not improve SCI dysesthetic pain.
