Table 1.
List of therapeutic drugs involved in management of PDN. (-) shows decrease in the level of that component, and (+) shows increase in the level of that component.
| Sr | Drugs | Target | Observation | Clinical or Preclinical | References |
|---|---|---|---|---|---|
| 1 | Epalrestat | Polyol pathway | Spontaneous pain (-), MNCV (+), SNCV (+), vibration perception threshold (+), F-wave latency (-) | Clinical and preclinical | [22, 162] |
| 2 | Sorbinil | Polyol pathway | Polyol pathway (-), Na pump defect (-), defective axonal transport (-), NCV (+), myelinated fiber repair (+) | Preclinical and clinical | [163, 164] |
| 3 | Fidarestat | Polyol pathway | Sorbitol accumulation (-), spontaneous pain (-), median nerve FCV (-), minimal latency (-), NCV (+) | Clinical | [14, 165] |
| 4 | Zenarestat | Polyol pathway | Nerve conduction velocity (NCV) (+), sorbitol in sciatic nerve (-) | Clinical and preclinical | [165, 166] |
| 5 | Tolrestat | Polyol pathway | MNCV (+), polyol influx in nerve (+), neuropathic pain (-) | Clinical | [167] |
| 6 | Benfotiamine | Hexosamine pathway | Pain (-) when coadministered with alpha lipoic acid | Clinical | [32] |
| 7 | Berberine | PKC pathway, MAPK pathway, TNF-alpha, oxidative stress, TRPV1 | Thermal hyperalgesia (-), mechanical hyperalgesia (-) | Preclinical | [36] |
| 8 | Vitamin D | AGE | Pain (-) neuroprotective effect on Schwann cells (+), | Clinical and preclinical | [39, 42] |
| 9 | Pyridoxamine | RAGE/NF-kB/ERK | Mechanical allodynia (-) | Preclinical | [74] |
| 10 | Compound XiongShao Capsule | AGEs | Thermal hyperalgesia (-), mechanical hyperalgesia (-), | Preclinical | [45] |
| 11 | Tocotrienol | ROS | Reversed PDN when administered in combination with insulin | Preclinical | [46] |
| 12 | Tribulus terrestris extract | ROS, inflammatory mediators | Pain threshold (+) | Preclinical | [50] |
| 13 | Fisetin | ROS, NF-κB, | Thermal and mechanical pain (-) | Preclinical | [51] |
| 14 | Rosmarinus officinalis L. | ROS | Antinociceptive (+), anti-neuropathic (+) | Preclinical | [52] |
| 15 | Kaempferol extracted from Eruca sativa | ROS | Partial pain reduction | Preclinical | [53] |
| 16 | Alpha lipoic acid | NF-κB, ROS, TRPV1 | Hyperalgesia (-), reduced glutathione (+) | Clinical | [54–56] |
| 17 | Acetyl L-carnitine | ROS | Mechanical allodynia (-), synaptic glutamate level (-), NCV (+), nerve regeneration (+) | Clinical | [58, 60, 61] |
| 18 | 1,5-Isoquinolinediol | PARP inhibitor | Thermal hyperalgesia (-), tactile allodynia (-), mechanical hyperalgesia (-) | Preclinical | [64] |
| 19 | 10-(4-Methylpiperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one | PARP inhibitor | Intraepidermal nerve fiber degeneration (-), partial reduction of pain (+) | Preclinical | [65] |
| 20 | SB203580 | p38a MAPK inhibitors | Mechanical allodynia (-), hyperalgesia (-) | Preclinical | [67–69] |
| 21 | SD-282 | ||||
| 22 | SP600125 | JNK inhibitor | |||
| 23 | U0126 | MAPK inhibitor | |||
| 24 | Ziziphus jujuba Root bark | NF-κB, ROS | Thermal hyperalgesia (-), mechanical hyperalgesia (-), cold allodynia (-) | Preclinical | [73] |
| 25 | Desert Hedgehog deficiency | Hedgehog pathway | Thermal hyperalgesia (-) | Preclinical | [77] |
| 26 | Minocycline | Cytokines, PARP | Neuropathic pain (-) in combination with morphine | Preclinical | [82] |
| 27 | Curcumin derivative J147 | AMP kinase pathway, TNF-α | Touch triggered allodynia (-) | Preclinical | [84] |
| 28 | Nimesulide | COX-2 | Pain threshold (+) when administered in combination with rutin | Preclinical | [87] |
| 29 | Celecoxib | COX-2 | Allodynia (-), hyperalgesia (-) | Preclinical | [88] |
| 30 | Meloxicam | COX-2 | Allodynia (-) | Preclinical | [89] |
| 31 | SC-58125 and NS-398 | COX-2 | Hyperalgesia (-) | Preclinical | [90] |
| 32 | Endogenous NGF | NGF | Pain relief in phase II, but no statistically significant pain relief in phase III trials | Clinical | [100–102] |
| 33 | Exogenous NGF | NGF | Mechanical pain threshold (+) | Preclinical | [99] |
| 34 | Lycium barbarum polysaccharide | Autophagy, mTOR/p70S6K, | Pain thresholds (+) | Preclinical | [106] |
| 35 | NONRATT021972 siRNA | Long nonprotein coding | ATP activated currents (-), spontaneous pain (-), P2X7 (-), TNF-alpha (-), GFAP (-) | Preclinical | [111] |
| 36 | uc.48+ siRNA | Long nonprotein coding | Spontaneous pain (-), proinflammatory cytokines (-) | Preclinical | [66, 168] |
| 37 | BC168687 siRNA | Long nonprotein coding | Preclinical | [169] | |
| FDA/EU-approved drugs | |||||
| 1 | Pregabalin | α 2-δ ligand | Neuropathic pain (-) | Clinical | [136] |
| 2 | Duloxetine | SNRI inhibitor | Neuropathic pain (-) | Clinical | [124] |
| 3 | Tapentadol ER | Mu-opioid receptor agonist and norepinephrine reuptake inhibitor. | Pain reduction (+) | Clinical | [153] |
| 4 | Capsaicin | TRPV1 agonist | Pain sensitivity (-) | Clinical | [156] |
| Topical drugs | |||||
| 1 | Lidocaine | Blockers of voltage-gated Na+ channels | Na+ ion influx (-), pain transduction pathway (-) | Clinical | [117] |
| 2 | Nitrate | NO donor | NO (+), vasodilation (+) | Clinical | [121] |
MNCV: motor nerve conduction velocity; NCV: nerve conduction velocity.