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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