Table 4.
Effects of curcumin on sciatic nerve crush injury (SNC), spared nerve injury (SNI), and sciatic nerve ligation (SNL).
| Animals (Sex, Strain) | Dose (mg/kg), Route of Administration, Duration of Treatment | Effects | Reference | ||
|---|---|---|---|---|---|
| Behavioral/Other | Electrophysiological/ Functional |
Histopathological/ Biochemical/Molecular |
|||
| Sciatic Nerve Crush (SNC) Injury | |||||
| Male Sprague-Dawley rats | SNC + curcumin dissolved in polyethylene glycol 300 at a concentration of 0.035 mg/µL, 0.2 mg/day osmotic minipump infusion, 28 days |
✓ Mechanical (von Frey), finger spacing of injured paw (visual static sciatic index), skillful walking (beam walking task test), grip strength (grip strength test) |
↑ MNCV and SNCV | ↑ Myelin sheath thickness ↑ MPZ and PMP22 expressions ↓ Neurogenic lesions ↓ Macrophage-induced production of ROS, lipid peroxidation ↑ Transcription factor Nrf2 expression |
[150] |
| Female Wistar Albino rats | SNC + curcumin (100 mg/kg, nasogastric tube, 28 days) | Not tested | ↑ SFI values ✓ Amplitude values and latency time O Gastrocnemius muscle weight |
O G ratios ✓ Myelin thickness, axon diameter, and nerve diameter |
[154] |
| Male Sprague-Dawley rats | SNC + curcumin (50, 100, 300 mg/kg, i.p., 4 weeks) | ↑ Mechanical withdrawal threshold (von Frey) ↓ Thermal withdrawal threshold (hotplate) |
↑ SFI values ✓ NCV, CMAP latency onset and peak amplitude ↓ Atrophy of gastrocnemius muscle |
↑ Number of fluoro-gold-positive neurons ↑ Number of myelinated axons per nerve transverse section and mean diameter of nerve fibers |
[152] |
| Female Sprague-Dawley rats | SNC + curcumin (100 mg/kg, gavage, 28 days) | Not tested | Not tested | ↓ Decreased volume of ganglion, mean cell volume, total volume of DRG cells (A- and B-cells), total surface of DRG cells, total number, diameter, and area of myelinated nerve fibers | [153] |
| Combination Study | |||||
| Male Wistar rats | SNC + curcumin (100 mg/kg, i.p., 4 weeks) + melatonin (10 mg/kg, i.p., 4 weeks) during light (9 am) and dark (9 pm) periods | Not tested | Light and dark curcumin ✓ SFI Dark melatonin group ✓ SFI Light and dark curcumin O Amplitudes and conduction latencies of evoked CMAP recorded in gastrocnemius muscle Curcumin ✓✓ Shortest latency and greatest amplitude Light and dark curcumin ✓✓ Smallest gastrocnemius muscle atrophy Dark melatonin ✓✓ Gastrocnemius muscle mass |
Light and dark curcumin ✓✓ Lesser TOS Light and dark curcumin ✓✓ Higher color intensity of nerve myelin staining (Luxol Fast Blue staining) Dark melatonin ✓✓ Higher nerve myelin staining Light and dark curcumin ✓✓ Higher number of Schwann cells Light curcumin ✓✓ Increased number of neurofilament-positive stained areas Dark melatonin ✓✓ Better neurofilament-positive stained areas |
[151] |
| Spared Nerve Injury (SNI) | |||||
| Male Sprague-Dawley rats | SNI + curcumin (100 mg/kg, i.p., 4 weeks) SNI + PI3K inhibitor LY294002 (30 mg/kg, i.p., 10 min before curcumin administration) + curcumin (100 mg/kg, i.p., 4 weeks) SNI + siNGF (1ng in 5µL, i.t., 10 min before curcumin administration) + curcumin (100 mg/kg, i.p., 4 weeks) In vitro: 30 mM |
Not tested | Not tested |
✓ PC-12 neurons against H2O2-induced apoptosis by ↑ TrkA, Akt and ↓ p17 ↓ pro-NGF but ↑ mature NGF level PI3K/Akt inhibition ↑ Apoptotic rate by decreasing p17, Ki67, and cyclin D1 NGF suppression and PI3K inhibition ↑ Neuron cell death by increasing proNGF and decreasing mNGF, Akt, TrkA, p75NTR, and p17 |
[158] |
| Male BALB/c mice | SNI or sham + curcumin (30, 60, 120 mg/kg, i.p., twice daily from day 1 until day 7 after surgery) | ↓ Mechanical (von Frey) and cold (acetone test) allodynia | Not tested |
X IL-1β protein level X NALP1 inflammasome aggregation and JAK2-STAT3 cascade activation in astrocytes |
[159] |
| Spinal Nerve Ligation (SNL) | |||||
| Female Wistar rats | SNL or sham + curcumin (30, 100, 200, and 300 μg, i.t., 14 days after surgery) SNL or sham + curcumin (10, 100, 310 mg/kg, oral, 14 days after surgery) |
X SNL-induced mechanical allodynia (von Frey) Curcumin + Inhibitors-NO synthase (L-NAME), guanylyl cyclase (ODQ), and ATP-sensitive K+ channel (glibenclamide) X anti-allodynic activity |
Not tested | [160] | |
| Sprague-Dawley rats, sex not specified | SNL + curcumin (200 μg, i.t., 7th, 8th, 9th, 10th, 15th, and 20th day after surgery) | ↓ SNL-induced mechanical allodynia (von Frey) from 10th day post-treatment | Not tested | Not tested | [161] |
Behavioral modalities are mentioned within parentheses. ✓ = protect/improved; ✓✓ = exert/induce; ↑ = increase/upregulate; ↓ = decrease/downregulate; O = no difference; X = prevented/inhibited; CMAP = compound muscle action potential; DRG = dorsal root ganglion; H2O2 = hydrogen peroxide; IL-1β = interleukin-1β; i.p. = intraperitoneal; i.t. = intrathecal; JAK2-STAT3 = Janus kinase 2-signal transducer and activator of transcription 3; MNCV = motor nerve conduction velocity; MPZ = myelin protein zero; NALP1 = NAcht leucine-rich-repeat protein 1; NCV = nerve conduction velocity; NGF = nerve growth factor; Nrf2 = nuclear factor erythroid 2–related factor 2; PI3K/Akt = phosphatidylinositol 3-kinase/Akt protein kinase B; PMP22 = peripheral myelin protein 22; ROS = reactive oxygen species; SFI = sciatic functional index; SNC = sciatic nerve crush; SNCV = sensitive nerve conduction velocity; SNI = spared nerve injury; SNL = spinal nerve ligation; TrkA = tropomyosin receptor kinase A.