Table 4.

Analgesic Medication for Post-SCI Pain

Author Year Country Score (PEDro/D&B)	Population	Intervention	Results
Lidocaine
Finnerup et al. 200553 Denmark RCT PEDro=10	N:24 Type of pain: Individuals with neuropathic pain	Treatment: 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. Pain Scale: MPQ	In the total sample of patients, lidocaine reduced pain vs. placebo (p<0.01). Assessing those with and without evoked, lidocaine still superior to placebo at reducing pain (p<0.01 and p<0.048, respectively). More patients reported pain relief with at level and below-level pain while receiving lidocaine vs. placebo.
Attal et al. 200052 France RCT PEDro=10	N:16 Type of pain: Individuals with neuropathic pain	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. Pain Scale: VAS, MPQ	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). More people received pain relief with lidocaine than with placebo; however, relief waned by 60 min post injection. Lidocaine reduced pain in 11 patients; and, in 6 of 12 patients, burning pain totally or partially relieved. 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. 200455 Sweden RCT PEDro=10	N:10 Type of pain: Individuals with neuropathic pain	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	VAS scores were significantly reduced in ketamine vs. the placebo group (p<0.01). Comparing lidocaine and placebo group, no significant difference noted (p=0.60). Pain relief was not linked to altered temperature thresholds or other changes in sensory function.
Loubser & Donovan 199151 USA RCT PEDro=8	N:21 Type of pain: Not stated	Treatment: SCI patients with pain received 2 separate injections (placebo vs. 5% lidocaine in dextrose) through a lumbar subarachnoid catheter. Pain Scale: VAS	All 21 patients tolerated injections (anaesthetics and placebo) well. 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. Pain reduction post injection significant (p<0.01) for the treatment group only
Ketamine
Kvarnstrom et al.,200455 Sweden RCT PEDro=10	N:10 Type of pain: Individuals with neuropathic pain	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	VAS scores were significantly reduced in ketamine vs. the placebo group (p<0.01). Comparing lidocaine and placebo group, no significant difference noted (p=0.60). Pain relief was not linked to altered temperature thresholds or other changes in sensory function.
Eide et al., 199556 Norway RCT PEDro=7	N:9 Type of pain: Individuals with neuropathic pain	Treatment: SCI patients were given ketamine hydrochloride, alfentanil or a placebo as combination of bolus and continuous IV infusions. Bolus dose was administered for 60 seconds and the continuous intravenous infusion started simultaneously for 17 to 21 minutes while testing was performed. Pain Scale: VAS	Freidmann’s two-way analysis by ranks revealed differences between various treatments (p=0.005). Alfentanil and ketamine were significantly better than placebo (p<0.01 & p<0.04, respectively) No significant differences were noted between ketamine and alfentanil (Wilcoxon p=0.19). Significant differences were noted between the treatment groups (p=0.008). Allodynia was not changed more with ketamine vs. alfentanil (Wilcoxon p=0.93). Alfentanil reduced wind-up-like pain (p=0.014) compared to placebo. On ketamine, wind-up-like pain was not significantly reduced (p=0.07). A high correlation between the serum concentration of ketamine and the size of reduction in continuous pain (r=0.78, p<0.002) and reduction in wind-up-like pain (r=0.83, p<0.002) was noted.
Alfentanil
Eide et al., 199556 Norway RCT PEDro=7	N:9 Type of pain: Individuals with neuropathic pain	Treatment: SCI patients were given ketamine hydrochloride, alfentanil or a placebo as combination of bolus and continuous IV infusions. Bolus dose was administered for 60 seconds and the continuous intravenous infusion started simultaneously for 17 to 21 minutes while testing was performed. Pain Scale: VAS	Freidmann’s two-way analysis by ranks revealed differences between various treatments (p=0.005). Alfentanil and ketamine were significantly better than placebo (p<0.01 & p<0.04, respectively) No significant differences were noted between ketamine and alfentanil (Wilcoxon p=0.19). Significant differences were noted between the treatment groups (p=0.008). Allodynia was not changed more with ketamine vs. alfentanil (Wilcoxon p=0.93). Alfentanil reduced wind-up-like pain (p=0.014) compared to placebo. On ketamine, wind-up-like pain was not significantly reduced (p=0.07). A high correlation between the serum concentration of ketamine and the size of reduction in continuous pain (r=0.78, p<0.002) and reduction in wind-up-like pain (r=0.83, p<0.002) was noted.
Clonidine/Morphine
Siddal et al. 200062 Australia RCT PEDro=8	N:8 Type of pain: Individuals with neuropathic pain	Treatment: Placebo, morphine or clonidine was delivered via catheter into lumbar intrathecal space in 8 SCI patients. Each was first given either: 0.2–1mg of morphine, 50 to 100 mcg of clonidine or placebo; dosage increased if the subject had no side effects and no pain relief. Patients could receive up to 1.5-times the initial drug dosage if necessary. Once each received satisfactory pain relief (or developed side effects from drug they were on), he or she was given a mixture of morphine and clonidine. Pain Scale: NPRS, VPR	The administration of morphine or clonidine resulted in a mean reduction in pain levels; however, this was not statistically significant compared to the effects of placebo. When mixture of morphine and clonidine was administered, there was a significant reduction in pain vs. that achieved on placebo (p=0.008).
Uhle et al. 200063 Germany Prospective Controlled Trial D&B=9	N:10 Type of pain: Mixed group	Treatment: Subjects were implanted with an intrathecal pump, originally were given 3 ml saline followed by 1 ml morphine; this was followed by a second dose of morphine (0.02 mg) provided that no side effects or benefits had been noted. This was followed by clonidine (30 ug in 1 ml); then, depending on side effects, a final dose of Clonidine (50 ug in 1 ml). Pain Scale: VAS	Subjects reported good to excellent pain reduction following clonidine administration. After clonidine bolus, subjects experienced the optimum pain reduction. Average initial dose of clonidine was 53 ug/day; this decreased (or stabilized) to 44 ug/day.
Morphine
Attal et al. 200264 France RCT PEDro=10	N:15 Type of pain: Mixed group	Treatment: Initially, patients received IV morphine titrated up to the maximal tolerated dosage using successive bolus injections of 2 mg morphine every 10 minutes. Double blind phase began 3 weeks after titration phase. IV morphine or saline was administered. Pain Scale: VAS	Spontaneous pain scores decreased immediately after the end of the infusion of morphine and placebo for up to 120 minutes in both group. The effects of the morphine did not differ significantly from those who were given the placebo post injection. Those who reported pain relief from the treatment was higher (3x) after the morphine than after the placebo was given from 15 to 60 minutes post injection. Burning pain was weakened by the morphine in 7 pts and by placebo in 4 pts. When looking at the effects of morphine on mechanical allodynia it could be seen that the morphine produced a reduction in intensity. The saline treatment did not have an effect. The morphine significantly reduced (p<0.01) dynamic mechanical allodynia but not other pains.
Tramadol
Norrbrink & Lundeberg 200965 Sweden RCT PEDro=8	N:35 Type of pain: Individuals with neuropathic pain	Treatment: Patients were randomized in a 2:1 ratio (tramadol/placebo) and treatment was administered for 4 weeks. Both patients and staff were blind to the treatments. Each patient was given 50mg tramadol or placebo 3 times daily. The daily dose was increased by 1 tablet every 5 days to a max dose of 8 tablets. Pain Scale: MPI-S	Significant differences were seen in between group pain ratings (p<0.05). Patient Global Impression of Change rating was significantly higher in the tramadol group than the control group. Significant improvements were seen in ratings of anxiety, global life satisfaction and sleep quality (p<0.05). No significant changes were seen in pain pleasantness, depression, or on the MPI scales pain interference, perceived life control, affective distress or social support.
Mexiletine
Chiou-Tan et al. 199654 USA RCT PEDro=8	N:15 Type of pain: Individuals with neuropathic pain	Treatment: Following a 1-week washout period, SCI subjects given either 150 mg of mexiletine or placebo (150mg-3 × daily) followed by another 1-week washout period; subjects then crossed over to opposite treatment. Pain Scale: VAS, MPQ	No significant inter-group differences in average pain over preceding week or pain at time of testing. No difference in McGill Pain scores. No changes in level of function.
Capsaicin
Sandford et al., 200067 USA Case Studies D&B=4	N:8 Type of pain: Not stated	Treatment: Charts reviewed for individuals given capsaicin to reduce pain. Pain Scale: Not stated	Patients reported a reduction in pain following the administration of capsaicin.

Abbreviations: D&B = Downs and Black quality assessment scale score²⁷ ;IV = Intravenous; MPI-S = Multidimensional Pain Inventory MPQ = McGill Pain Questionnaire; NPS = Neuropathic Pain Scale; NPSI = Neuropathic Pain Symptom Inventory; NRS = 11 Point Numeric Rating Scale; PEDro = Physiotherapy Evidence Database rating scale score²⁶; VAS = Visual Analogue Scale; VPR = Verbal Pain Rating