Table 1.
Summary of preclinical evidence examining the impact of exercise training on neuropathic nociception
| Study | Pain model | Exercise modality | Exercise program duration | Exercise Session (frequency and duration) | Exercise Intensity | Mechanism | Outcome |
|---|---|---|---|---|---|---|---|
| Kuphal et al. (2007) [16] | SNI | Swimming | Varied | 90 min/day | Not indicated | NA |
↓ Cold allodynia ↓ Thermal hyperalgesia |
| Cobianchi et al. (2010) [17] | SNI | Treadmill running |
1 week 8 weeks |
5 days/week 60 min/day |
20–52 cm/s | Microglia |
↓ Mechanical allodynia (1 week) ↔ Mechanical allodynia (8 weeks) |
| Bobinski et al. (2011) [18] | SNI | Treadmill running | 2 weeks |
5 days/week 30 min/day |
10 m/min | Inflammation |
↓ Mechanical hypersensitivity ↓ Cold hypersensitivity |
| Chen et al. (2012) [19] | SNI |
Treadmill running Swimming |
6 weeks 39 days |
5 days/week 60 min/day 7 days/week 90 min |
2–1.8 km/h | HSP72 and inflammation |
↓ Heat sensitivity ↓ Mechanical allodynia |
| Shen and Cheng (2013) [20] | SNI | Swimming | 4 weeks |
5 days/week 60 min/day |
Not indicated | NA |
↓ Mechanical allodynia ↓ Thermal allodynia |
| Almeida et al. (2015) [21] | SNI | Swimming | 5 weeks |
5 days/week 10–50 min/day |
Not indicated | Microglia, neurotrophins | ↓ Mechanical hypersensitivity |
| Bobinski et al. (2015) [22] | SNI | Treadmill running | 2 weeks |
5 days/week 30 min/day |
10 m/min | Serotonin | ↓ Mechanical hypersensitivity |
| Kim et al. (2015) [23] | SNI | Treadmill running | 4 weeks |
5 days/week 30 min/day |
8–22 m/min | Endogenous opioid system |
↓ Mechanical allodynia ↓ Thermal allodynia |
| Lόpez- Àlvarez et al. (2015) [24] | SNI | Treadmill running |
5 sessions 9 sessions |
5 days/week 60 min/day |
10–32 cm/s | Neurotrophins |
↓ Mechanical hyperalgesia (5 and 9 session) ↓ Heat hyperalgesia (5 session) |
| Sheahan et al. (2015) [25] | SNI | Wheel running | 2 weeks | Voluntary | Voluntary | NA | ↔ Mechanical allodynia |
| Grace et al. (2016) [26] | SNI |
Wheel running (prior to injury) |
6 weeks | Voluntary | Voluntary | Microglia and inflammation | ↓ Mechanical allodynia |
| Kami et al. (2016) [27] | SNI | Treadmill running | 1 week |
5 days/week 60 min/day |
7 m/min | GABA |
↓ Mechanical allodynia ↓ Heat hyperalgesia |
| Kami et al. (2016) [28] | SNI | Treadmill running | 1 week |
5 days/week 60 min/day |
7 m/min | Microglia |
↓ Mechanical allodynia ↓ Heat hyperalgesia |
| Wakaizumi et al. (2016) [29] | SNI | Treadmill running | 2 weeks |
5 days/week 60 min/day |
6 m/min 12 m/min |
Dopamine |
↓ Tactile allodynia (both) ↓ Thermal hyperalgesia (both) |
| Safakhah et al. (2017) [30] | SNI | Treadmill running | 3 weeks |
5 days/week 30 min/day |
16 m/min | Inflammation |
↓ Mechanical allodynia ↓ Thermal allodynia |
| Tsai et al. (2017) [31] | SNI | Treadmill running | 3 weeks |
7 days/week 30 min/day |
14–16 m/min @ 8% grade | Inflammation |
↓ Mechanical allodynia ↓ Heat allodynia |
| Bobinski et al. (2018) [32] | SNI | Treadmill running | 2 weeks |
5 days/week 30 min/day |
10 m/min | Inflammation, microglia, neurotrophins | ↓ Mechanical hyperalgesia |
| Lόpez- Àlvarez et al. (2018) [33] | SNI | Treadmill running | 12 days | 60 min/day | 10–32 cm/s | Adrenergic and serotonin systems |
↓ Mechanical allodynia ↓ Thermal allodynia |
| Sumizono et al. (2018) [34] | SNI | Treadmill running | 5 weeks |
5 days/week 30 min/day 3 days/week 30 min/day |
20 m/min | Microglia, neurotrophin, endogenous opioid system | ↓ Mechanical sensitivity (both) |
| Hutchinson et al. (2004) [35] | SCI |
Treadmill running Swim training |
7 weeks |
5 days/week 20–25 min/day |
Not indicated | Neurotrophins |
↓ Mechanical hyperalgesia (all) ↓ Mechanical allodynia (treadmill) ↓ Mechanical allodynia- transient (swim) |
| Stagg et al. (2011) [36] | SCI | Treadmill running | 5 weeks |
5 days/week 30 min/day |
14–16 m/min @ 8% grade | Endogenous opioids |
↓ Mechanical allodynia ↓ Heat allodynia |
| Detloff et al. (2014) [37] | SCI | Forced running wheel | 6 weeks |
5 days/week 20 min/day |
5–14 m/min | Neurotrophins |
↓ Tactile allodynia ↔ Thermal hyperalgesia |
| Ward et al. (2014) [38] | SCI | Body weight supported treadmill running | 81 days |
7 days/week 58 min/day |
10–22 cm/s | Neurotrophins | ↓ Mechanical allodynia |
| Dugan and Sagan (2015) [39] | SCI | Treadmill running | 15 weeks |
5 days/week 10–40 min/day |
11–15 m/min @ 8° incline |
NA |
Prevention of heat hyperalgesia and cold allodynia ↓ Mechanical allodynia ↓ Heat hyperalgesia ↓ Cold allodynia |
| Detloff et al. (2016) [40] | SCI | Forced running wheel (delayed exercise) | 5 weeks |
5 days/week 20 min/day |
6–14 m/min | NA |
↔ Mechanical allodynia (animals with allodynia pre-exercise) ↑ Mechanical allodynia (animals without allodynia pre-exercise) |
| Nees et al. (2016) [41] | SCI | Treadmill | 5 weeks |
2×/day 15 min/session 5 days/week |
Not specified | Fiber density |
↓ Mechanical allodynia ↔ Heat hyperalgesia ↔ Loss of cold sensitivity (hypoalgesia) |
| Ward et al. (2016) [42] | SCI | Bodyweight supported treadmill training | 6 weeks |
6 days/week 30 min/day |
22 cm/s | NA | ↔ Mechanical allodynia |
| Gong et al. (2017) [43] | SCI (infant) | Wheel running | Unclear | 7 days/week | Voluntary | Microglia, inflammation | NA |
| Chhaya et al. (2019) [44] | SCI | Forced running wheel | 4 weeks |
5 days/week 20 min/day |
14 m/min | Macrophages | ↔ Mechanical allodynia |
| Dugan et al. (2020) [45] | SCI | Treadmill running | 10 weeks |
5 days/week 10–40 min/day |
10–15 m/min @ 80 incline | Inflammation |
Prevention of mechanical allodynia, heat hyperalgesia, and cold allodynia ↓ Mechanical allodynia ↓ Heat hyperalgesia ↓ Cold allodynia |
| Groover et al. (2013) [46] | High-fat diet (Pre-diabetes) | Voluntary wheel running | 12 weeks | Voluntary | Voluntary | Neurotrohpins and epidermal innervation |
↓ Mechanical allodynia ↔ Thermal allodynia |
| Rossi et al. (2011) [47] | DPN | Group swimming | 8 weeks |
7 days/week 10–60 min/day |
Not indicated | NA | ↓ Thermal hyperalgesia |
| Shankarappa et al. (2011) [48] | DPN | Treadmill running | 10 weeks |
5 days/week 60 min/day |
18 m/min | Endogenous opioid system | ↓ Mechanical allodynia |
| Chen et al. (2013) [49] | DPN | Treadmill Running | 8 weeks | Daily | 20–25 m/min | HSP72 |
↓ Mechanical hypersensitivity ↓ Heat hypersensitivity |
| Aghdam et al. (2018) [50] | DPN | Swimming | 10 weeks |
5 days/week 60 min/day |
Not indicated | miR-96 | ↓ Thermal pain threshold |
| Golbar et al. (2018) [51] | DPN | Treadmill running | 6 weeks |
5 days/week 10–30 min/day |
10–18 min/min | Motor proteins |
↓ Mechanical allodynia ↓ Thermal hyperalgesia |
| Ma et al. (2018) [52] | DPN | Treadmill running | 5 weeks |
4 days/week 10 min/day |
5–10 m/min @ 10% grade | Inflammation | ↓ Mechanical hyperalgesia |
| Martins et al. (2013) [53] | CRPS Type I | Swimming | 4 weeks |
7 days/week 50 min/day |
Not indicated | Endogenous opioid and adenosinergic systems | ↓ Mechanical allodynia |
| Park et al. (2015) [54] | CIPN | Treadmill running | 4 weeks |
7 days/week 50 min/day |
10 m/min | Epidermal innervation | Exercised mice did not develop thermal hypoalgesia. |
| Slivicki et al. (2019) [55] | CIPN | Voluntary wheel running | 23–28 days | 7 days/week | Voluntary | NA |
Mice who exercised before and during Paclitaxel treatment did not develop mechanical or cold allodynia Mice who ran before Paclitaxel had delayed onset of mechanical and cold allodynia Mice who ran during Paclitaxel treatment had less cold allodynia. |
Studies are grouped by pain model then organized chronologically. CIPN Chemotherapy-induced peripheral neuropathy, CRPS Complex regional pain syndrome, DPN Diabetic peripheral neuropathy, SNI Sciatic nerve injury, SCI Spinal cord injury, ↓ = lower NPP outcome in exercised mice compared to sedentary, ↑ = higher NPP outcome in exercised mice compared to sedentary, ↔ = no differences in NPP outcome between groups