Table 1.
Summary of studies in which IL-10-based therapy was used in animal models of neuropathic pain.
| Neuropathic Pain
| |||||||
|---|---|---|---|---|---|---|---|
| Model | Sex | Treatment | Dose/route | Time of treatment | Effect | Duration of effect | Reference |
| SD rats (CCI) | Female | IL-10 (n/s) | 250 ng, peri-sciatic nerve | 0 DPI | ↓ Thermal hyperalgesia | ~7 days | Wagner et al., 1998 |
| SD rats (CCI) | Male | hIL-10 | 50 –> 500 – > 500 ng, IT | 10 –> 11 –> 12 DPI | ↓ Mechanical allodynia (each injection) ↓ Thermal hyperalgesia (2nd/3rd injection) |
~2 h | Milligan et al., 2005a |
| SD rats (CCI) | Male | AD-hIL-10 | 5 × 107 PFU, IT | 10 DPI | ↓ Mechanical allodynia ↓ Thermal hyperalgesia |
~10 days (mechanical allodynia) ~3–5 days (thermal hyperalgesia) |
Milligan et al., 2005a |
| SD rats (SIN) | Male | AD-hIL-10 | 5 × 107 PFU, IT | Immediately pre-zymosan injection | ↓Mechanical allodynia | 24 h (ET) | Milligan et al., 2005a |
| SD rats (SIN) | Male | AD-hIL-10 | 5 × 107 PFU, IT | 1 day post-zymosan injection | ↓Mechanical allodynia | ~3 days (ET) | Milligan et al., 2005a |
| SD rats (CCI) | Male | AAV2-rIL-10 | 8.5 × 108 IPs, IT | 10 DPI | ↓Mechanical allodynia/thermal hyperalgesia | ~12 days (allodynia) ~14 days (thermal hyperalgesia) |
Milligan et al., 2005b |
| SD rats (SIN) | Male | AAV2-rIL-10 | 8.5 × 108 IPs, IT | 2 days pre-zymosan | ↓Mechanical allodynia | ~7–8 days | Milligan et al., 2005b |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 μg × 4, IT | 10 –> 14 –> 22 – > 64 DPI | ↓Mechanical allodynia | Each injection lasted until subsequent injection, final injection 5 days (ET) | Milligan et al., 2006a |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 μg × 2, IT | 10 –> 13 DPI | ↓Mechanical allodynia | ~45–47 days (ET) | Milligan et al., 2006a |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 μg × 2, IT | 58 –> 61 DPI | ↓Mechanical allodynia | ~7–35 days (unreliable effect) | Milligan et al., 2006a |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 1 μg × 2, IT | 10 –> 13 DPI | No effect | N/A | Milligan et al., 2006b |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 μg × 2, IT | 10 –> 13 DPI | ↓Mechanical allodynia | ~31 days | Milligan et al., 2006b |
| SD rats (CCI) | Male | PEI-pDNA-rIL-10-F129S | 5 μg, IT | 10 DPI | ↓Mechanical allodynia | ~11 days | Milligan et al., 2006b |
| SD rats (CCI) | Male | PEI-pDNA-rIL-10-F129S | 5 μg × 2, IT | 10 –> 13 DPI | ↓Mechanical allodynia | ~27–30 days | Milligan et al., 2006b |
| SD rats (CCI) | Male | XT-101 | 400 ng, IT | 10 DPI | ↓Mechanical allodynia | ~28–29 days (ET) | Milligan et al., 2006b |
| SD rats (PIN) | Male | pDNA-rIL-10-F129S | 100 –> 25 μg, IT | 35 –> 38 DPI | ↓Mechanical allodynia | ~32–37 days | Ledeboer et al., 2007 |
| SD rats (CCI) | Male | Control pDNA – > pDNA-rIL-10-F129S | 100–>25 μg, IT | 10 –> 13 DPI | ↓Mechanical allodynia | ~89 days (ET) | Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S – > Control pDNA | 100 –> 25 μg, IT | 10 –> 13 DPI | ↓Mechanical allodynia | ~3–4 days | Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 –> 25 μg, IT | 10 –> 13 DPI | ↓Mechanical allodynia | ~93 days (ET) | Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 –> 1 μg, IT | 10 –> 13 DPI | ↓Mechanical allodynia | ~77–85 days | Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 –> 25 μg, IT | 10 DPI–>2 h post 1st injection | ↓Mechanical allodynia | ~6 days | Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 –> 25 μg, IT | 10 DPI–>5 h post 1st injection | ↓Mechanical allodynia | ~58 days (ET) | Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 125 μg, IT | 10 DPI | ↓Mechanical allodynia | ~6 days | Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 (pDNA) –> 0.2 (anti-IL-10) –> 25 (pDNA) μg, IT | 10 DPI–>1 h after 1st injection –>13 DPI | ↓Mechanical allodynia (pDNA) reversed acute/sustained pDNA antinociception (anti-IL-10) | ~1 day after each injection (pDNA) ~1 day/~29 days (ET) (anti-IL-10) |
Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 100 –> 25 μg (pDNA) –> 0.2 μg (anti-IL-10), IT | 10 –> 13 (pDNA) – > 23 (anti-IL-10) DPI | ↓Mechanical allodynia (pDNA) reversed sustained pDNA antinociception (anti-IL-10) | ~23 days (pDNA) ~31 days (ET) (anti-IL-10) |
Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 25 –> 25 –> 25 μg, IT | 10 –> 13–> 45 DPI | ↓Mechanical allodynia | Each injection lasted until subsequent injection, final injection 47 days (ET) | Sloane et al., 2009 |
| SD rats (CCI) | Male | pDNA-rIL-10-F129S | 25 –> 25 –> 25 μg, IT | 10 –> 13–> 61 DPI | ↓Mechanical allodynia | 1st and 2nd injections lasted ~28 days, final injection had no effect | Sloane et al., 2009 |
| SD rats (CCI) | Male | XT-101 (rat) | 8.8 μg, IT | 10 DPI | ↓Mechanical allodynia | ~73–81 days | Soderquist et al., 2010 |
| SD rats (SNI) | Male | rIL-10 | 0.5–5 μg, intra-red nucleus | 21 DPI | ↓Mechanical allodynia | 30–60 min | Wang et al., 2012 |
| SD rats (SCI) | Male | HSV-rIL-10 | 2 × 108 PFU, IPL | 7 DPI | ↓Mechanical allodynia/hyperalgesia and thermal hyperalgesia ↓Operant conflict avoidance |
~28 days (allodynia/hyperalgesia) (ET) *only tested on day 35 (operant conflict avoidance) |
Lau et al., 2012 |
| SD rats (L5/L6 SNL) | Male | rIL-10 | 0.1–1 μg, IT | 1–7 DPI (daily) (each injection 1 h before testing) | ↓Mechanical allodynia | N/A | Lee et al., 2013 |
| SD rats (L5/L6 SNL) | Male | rIL-10 | 7 μg, IT | 7 DPI (injection 1 h before testing) | No effect | N/A | Lee et al., 2013 |
| SD rats (L5 SNL) | Male | rIL-10 | 500 ng × 3, IT | 7 –> 8 –> 9 DPI (1×/day) | ↓Mechanical allodynia | ~2 h after each injection | Shen et al., 2013 |
| SD rats (L5 SNL) | Male | rIL-10 | 500 ng × 12, IT | 7 –> 8 –> 9 DPI (4×/day) | ↓Mechanical allodynia | ~8 days (ET) | Shen et al., 2013 |
| SD rats (CCI) | Male | D-mannose –> pDNA-rIL-10-F129S | 50 ug (D-mannose) –> 1 μg (pDNA) | 10 (D-mannose) – > 13 (pDNA) DPI | ↓Mechanical allodynia | ~10 days | Dengler et al., 2014 |
| SD rats (CCI) | Male | D-mannose –> pDNA-rIL-10-F129S | 50 ug (D-mannose) –> 25 μg (pDNA) | 10 (D-mannose) – > 13 (pDNA) DPI | ↓Mechanical allodynia | ~92 days (ET) | Dengler et al., 2014 |
| SD rats (CCI) | Male | D-mannose + pDNA-rIL-10-F129S | 50 ug (D-mannose) + 1 μg (pDNA) | 10 DPI | ↓Mechanical allodynia | ~23 days (ET) | Dengler et al., 2014 |
| Dog (N/S NP) | Mixed | XT-101 (human) | 500 μg, IT | Various | ↓Pain-related behaviors | ~4 months | Unpublished observations |
Abbreviations: ↓: suppression, –>: denotes sequence of injections, AAV: adeno-associated virus, AD: adenovirus, CCI: chronic constriction injury, DPI: days post-injury, ET: experiment terminated before resolution of antinociceptive effect, hIL-10: human IL-10, HSV: herpes simplex virus, IPs: infectious particles, IPL: intraplantar, IT: intrathecal, N/S NP: non-specified neuropathic pain, pDNA: plasmid DNA, PEI: polyethylenimine, PIN: paclitaxel-induced neuropathy, PFU: plaque-forming units, PLGA: poly(lactic-co-glycolic), SCI: T12 blunt laminectomy, SD rat: Sprague–Dawley rat, SIN: sciatic inflammatory neuropathy, SNI: spared nerve-injury, SNL: spinal nerve ligation, rIL-10: rat IL-10 rIL-10-F129S: point mutation rIL-10 variant, xT-101 (rat): PLGA-rat IL-10-F129S, xT-101 (human): PLGA-human IL-10-F129S.