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Table 1 Summary of preclinical evidence examining the impact of exercise training on neuropathic nociception

From: Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research

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.
  1. 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