Lidocaine

Finnerup et al. 2005
Denmark
PEDro=10
RCT
N=24

Population: Type of pain=neuropathic
Treatment: 24 SCI patients participated. Subjects 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: 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.

Attal et al. 2000
France
PEDro=10
RCT
N=16

Population: Type of pain=neuropathic
Treatment: Patients participated, 6 who had had a stroke and 10 post SCI. Subjects given 5mg of lidocaine or saline over a 30-min period. Treatments given in separate sessions, 3 weeks apart. Order of sessions randomized.
Outcome Measures: VAS, MPQ

1. Effects of lidocaine on pain were greater than effects of placebo, starting at end of injection, and lasting for up to 45 minutes 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 minutes post injection.

Kvarnstrom et al. 2004
Sweden
PEDro=10
RCT
N=10

Population: Type of pain=neuropathic
Treatment: SCI patients were recruited for participation. Ketamine (0.4mg/kg) vs. lidocaine (2.5mg/kg) vs. saline placebo administered intravenously over 40 min.
Outcome Measures: 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.

Loubser & Donovan 1991;
USA
PEDro=8
RCT
N=21

Population: Age = 18-58 yrs; Gender: males = 15, females = 6; Level of injury: cervical, lumbar; Duration of chronic pain = >6 mths.
Treatment: Subjects had a lumbar subarachnoid catheter inserted. Subjects recorded their pain intensity at baseline. This was followed by 2 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 mins.
3. The decrease in pain reduction following lidocaine was significant (p<0.01) for the treatment group only.

Mexiletine

Chiou-Tan et al. 1996
USA
PEDro=8
RCT
Initial N=15; Final N=11

Population: Mean age = 44 yrs; Gender: males = 11, females = 2; Severity of injury: AIS: A-E; Time since injury = 7 yrs.
Treatment: Following a 1 wk washout period subjects were given either 150 mg of mexiletine or placebo (150mg-3 x daily) 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.

Ketamine

Kvarnstrom et al. 2004
Sweden
PEDro=10
RCT
N=10

Population: Type of pain=neuropathic
Treatment: SCI patients were recruited for participation. Ketamine (0.4mg/kg) vs. lidocaine (2.5mg/kg) vs. saline placebo administered intravenously over 40 min.
Pain 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
PEDro=7
RCT
N=9

Population: Age = 25-72 yrs; Gender: males = 8, females = 1; Level of injury: cervical, thoracic; Severity of injury: AIS: A-D; Onset of pain: <6 mths post injury, Length of pain: 14-94 mths.
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 to 21 minutes while the testing was performed.
Outcome Measures: Continuous pain was measured by a 100 mm visual analogue scale (no pain to unbearable pain (0 to 100)) before and after each drug treatment.

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 & 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.