Table 2.
Clinical studies promoting inhibitory tone for SCI-NP
| Approach and route | Duration | No. of participants | Mechanism and conclusion | |
|---|---|---|---|---|
| Mechanism and conclusion | ||||
| Ketamine (i.v. then p.o.) | 17.2 Days (acute), 59 days (subacute) | 13 | Ketamine reduced allodynia in acute phase significantly by antagonizing NMDA receptors [142] | |
| (Epidural injection) | 7-, 15-, 30, 45-, and 60-day postinjection | 40 | Showed effects till 30 days post injection by antagonizing NMDA receptors [143] | |
| Ketamine and Alfentanil (i.v. infusion) | - | 9 | Both markedly reduced evoked pain by antagonizing NMDA receptors [144] | |
| Ketamine (i.v.)+Lidocaine (i.v.) | - | 10 | NMDA antagonist ketamine but not lidocaine was effective [145] | |
| Valproic acid (p.o.) | 8 Weeks | 20 | Voltage-gated ion channels blocker showed no significant analgesic effects [146] | |
| Lamotrigine (p.o) | 9 Weeks | 30 | Pain reduction in patients with incomplete SCI by blocking sodium channels [71] | |
| Lamotrigine (p.o.) vs. amitriptyline (p.o.) | 3 Weeks | 147 | Sodium channel blocker and monoamine reuptake inhibitor both showed similar efficacy [73] | |
| Lidocaine (i.v.) | 1 to 3 weeks | 24 | Sodium channel blocker reduced pain at and below injury [66] | |
| 16 | ||||
| (5% plaster) | 160 Days | 1 | Superficial NP symptoms completely disappeared by blocking sodium channels [69] | |
| Lumbar subarachnoid catheterization | - | 21 | Response to diagnostic spinal anaesthesia using sodium channel blocker in chronic SCI pain is complex [147] | |
| Lidocaine (i.v.) vs. sodium amobarbital (i.v.) | - | 5 | Amobarbital by promoting GABAA inhibition was more superior in relieving pain [67] | |
| Mexiletine | 5 Weeks | 15 | Sodium channel blocker showed no significant pain reduction [148] | |
| Oxcarbazepine | - | 55 | Sodium channel blocker was more effective in patients without evoked pain [149] well tolerated, efficacious and safe for monotherapy | |
| 20 Weeks | 37 | |||
| Fosphenytoin (i.v.) vs. Lidocaine (i.v.) | - | 17 | Significant pain reduction by Sodium channel blocker fosphenytoin [150] | |
| Botulinum toxin type A (s.c.) | 4, 8, and 12 weeks | 40 | Showed significant pain reduction [75] and mainly controlled at-level SCI pain by inhibiting release of glutamate and substance P | |
| 8 | ||||
| Gabapentinoids | ||||
| Gabapentin (p.o.) | 4–24 Weeks | 7 | Decrease in pain intensity, burning sensation, [151] frequency and NP refractory to other analgesics by GABA modulation | |
| 31 | ||||
| 38 | ||||
| 20 | ||||
| Gabapentin (p.o.)+ketamine (infusion) | 4 Weeks | 40 | NMDA receptor antagonist ketamine was safe and efficacious adjuvant [65] | |
| Gabapentin+amitriptyline (p.o.) | 8 Weeks | 38 | Serotonin enhancer amitriptyline was more efficacious [152] | |
| Gabapentin vs. pregabalin (p.o.) | 8 Weeks | 30 | GABA analogs showed no difference in efficacy [153] | |
| Pregabalin (p.o.) | 9–17 Weeks | 137 | Pregabalin relieved moderate to severe NP [154] was effective and well tolerated [82] and also effective in NP related sleep interference [155] by GABA modulation | |
| 108 | ||||
| 175 | ||||
| 40 | ||||
| GABA agonist | ||||
| Baclofen (i.t.) | 24 Hours–12 months | 16 | GABAB agonist decreased chronic musculoskeletal pain but not chronic neurogenic pain, [156] suppressed spontaneous and evoked pain [157] and showed significant analgesic effect [98] | |
| 9 | ||||
| 13 | ||||
| KCC2 enhancer | ||||
| Bumetanide (p.o.) | 19 Weeks | 14 | Produced analgesia by upregulating KCC2 protein [55] | |
SCI, spinal cord injury; NP, neuropathic pain; CNP, chronic neuropathic pain; i.v., intravenous; p.o., peroral; NMDA, N-methyl-D-aspartate; GABA, gamma-aminobutyric acid; i.t., intrathecal; s.c., subcutaneous; KCC2, K+-Cl- cotransporter isoform 2.