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| First author, year | Article title | Pain model | Pain outcomes | HBO (depth, FiO2, duration, n of sessions) | Comparator | Timing of assessments, follow-up | Results |
| Pain outcomes | Other outcomes |
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| Li, F et al., 2011 [17] | Hyperbaric oxygenation therapy alleviates chronic constrictive injury-induced neuropathic pain and reduces tumor necrosis factor-alpha production | Chronic constrictive injury of the sciatic nerve (CCI) in rats | (i) Mechanical allodynia (MWT)
(ii) Cold allodynia | 2.4 ATA
100% FiO2
60 min
7 sessions (POD1-7) | 1 ATA
Room air
60 min
7 sessions (POD1-7) | MWT and cold allodynia tests on POD 4 and POD 7 | Compared to the CCI-only group, HBOT-treated rats exhibited a significant increase in MWT and decrease in cold allodynia response frequency at day 4 and day 7 | CCI-induced significant increase in TNF-α content in the sciatic nerve at days 4 and 7. This increase was significantly reduced in HBOT groups to near the level of sham rats |
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| Gu, N et al., 2012 [18] | Hyperbaric oxygen therapy attenuates neuropathic hyperalgesia in rats and idiopathic trigeminal neuralgia in patients | Chronic constrictive injury of the sciatic nerve (CCI) in rats | (i) Mechanical allodynia (MWT)
(ii) Thermal allodynia (TWL) | 1.5, 2.0, and 3.0 ATA
100% FiO2
70 min
7 sessions (POD1-7)
2 additional HBOT tx groups at 3.0 ATA receiving
3 sessions (POD14-16) and 7 sessions (POD 14–20) | 1.0 ATA
Room air
70 min
7 sessions | Multiple assessments of MWT and TWL from POD 0 to 28 | Compared to the CCI-only, 1.5 ATA, and 2.0 ATA HBOT groups, the 3.0 ATA HBOT group demonstrated a significant increase in MWT and TWL. The effect persistent throughout the assessment period (POD28). When HBOT treatment (3.0 ATA) was delayed for 2 weeks following CCI (only 3 HBOT sessions); there was a significant but transient (∼1 week) increase in MWT and TWL compared to CCI-only group. When HBOT treatments were extended to 7 sessions; this antinociceptive effect was sustained throughout the assessment period | Repetitive HBOT treatments suppressed the CCI-induced induction of c-fos and the activation of astrocytes in the rat spinal cord as well as the CCI-induced increased phosphorylation of NR2B, ERK, CaMKII, and CREB in the spinal cord |
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| Thompson et al., 2009 [19] | Hyperbaric oxygen treatment decreases pain in two nerve injury models | L5 nerve root ligation and chronic constrictive injury of the sciatic nerve (CCI) in rats | (i) Mechanical allodynia (MWT) | 2.4 ATA 100% FiO2 90 min
14 sessions (POD1-14) | 1.0 ATA
Room air
100 min
14 sessions (POD1-14) | MWT immediately following daily HBOT treatments (POD1-14) and then daily assessments for POD15-19 | Both CCI and L5 ligation groups exposed to HBOT demonstrated increased MWT at nearly every time point after the start of treatment compared to control rats and the effect persisted throughout the post-HBOT 5-day assessment period. Of the two HBOT groups, the CCI group responded to treatment sooner than the L5 ligation group and the treatment effect was maintained longer | |
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| Gibbons et al, 2013 [20] | Involvement of brain opioid receptors in the antiallodynic effect of hyperbaric oxygen in rats with sciatic nerve crush-induced neuropathic pain | Sciatic nerve crush injury | (i) Mechanical allodynia (MWT) | 3.5 ATA
100% FiO2
60 min
1 session (on POD7) | 1.0 ATA
Room air
60 min
1 session (on POD7) | MWT, every other day, up until POD30 | HBOT group demonstrated significant increase in mechanical threshold (as measured by AUC for changes in MWT from POD7-30) compared to CCI-only (control) rats and approached the threshold of sham | Intraventricular administration of naltrexone (following nerve crush injury and prior to HBOT treatment) completely blocked the antinociceptive effect of HBOT |
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| Zhao et al, 2015 [21] | Hyperbaric oxygen treatment at various stages following chronic constriction injury produces different antinociceptive effects via regulation of P2X4R expression and apoptosis | Chronic constrictive injury of the sciatic nerve (CCI) | (i) Mechanical allodynia (MWT)
(ii) Thermal allodynia (TWL) | 2.0 ATA
100% FiO2
60 min
5 sessions
3 treatment groups starting at different time points (HOB1 :
POD1-5, HBO6 POD6-10, and HBO11 :
POD11-15) | 1.0 ATA
Room air
60 min
5 sessions
3 control groups starting at different time points (POD1-5, POD6-10, and POD11-15) | MWT and TWL assessed on postop days 1, 3, 5, 7, 10, 14, and 21 | HBO1⟶significant increase in MWT and TWL following HBOT treatment and sustained for 21 days compared to CCI control
HBO6 ⟶ significant, but transient (<1 wk) improvement in MWT and TWL compared to CCI control
HBO11 ⟶ significant increase in MWT and TWL following HBOT treatment sustained for 10d compared to CCI control | HBOT early after injury (HBO1 group) inhibited the CCI-induced increase in expression of P2X4R (a ligand-gated ion channel activated by ATP and involved in the generation and maintenance of neuropathic pain). HBOT late after injury (HBO11) inhibited CCI-induced apoptosis via downregulation of caspase-3 |
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| Zhao et al, 2014 [22] | Hyperbaric oxygen treatment produces an antinociceptive response phase and inhibits astrocyte activation and inflammatory response in a rat model of neuropathic pain | Chronic constrictive injury of the sciatic nerve (CCI) | (i) Mechanical allodynia (MWT)
(ii) Thermal allodynia (TWL) | 2 groups: 2.0 ATA and 2.5 ATA
100% FiO2
60 min
7 sessions (POD1-7) | 1.0ATA
Room air
100 min
7 sessions (POD1-7) | Multiple daily MWT and TWL assessments throughout the HBOT treatment period: T0 = immediately following HBOT
T1 = 1 hr post-HBOT
T2 = 2 hr post-HBOT
T3 = before entering the HBOT chamber (following day) | T0 = decreased MWT and shortened TWL in both HBOT groups immediately after the first two HBOT sessions suggesting a transient allodynia with HBOT compared to CCI controls
T1 = increased MWT and lengthened TWL in both HBOT groups compared to CCI control during all 7 treatment days suggesting a rapid shift from transient allodynia to antinociceptive response following HBOT session. T3 = increased MWT and lengthened TWL only after 5 days of HBOT compared to CCI controls. This suggests that the antinociceptive response is initially transient but may become prolonged with repetitive HBOT treatments | After 7 d (but not 4 d) of HBOT, there was a significant decrease in the CCI-induced upregulation of IL-1b and IL-10 in the spinal cord. HBOT treatment groups also demonstrated a reduction in CCI-induced increase in GFAP-immunoreactive astrocytes at day 7 in the spinal dorsal horn. The results may suggest that repetitive HBOT suppresses proinflammatory (IL-1b) cytokines, expresses anti-inflammatory cytokines (IL-10), and decreases astrocyte activation in the spinal cord |
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| Han et al., 2013 [23] | Effects of hyperbaric oxygen on pain-related behaviors and nitric oxide synthase expression in
a rat model of neuropathic pain | Chronic constrictive injury of the sciatic nerve (CCI) | (i) Mechanical allodynia (MWT)
(ii) Thermal allodynia (TWL) | 2.4 ATA
FiO2 >90%
60 min
1 session either before or after CCI (POD-1 or POD + 1) | No control chamber treatment | MWT and TWL assessed on postop days 1, 2, 3, 7, 14, 21, and 28 | HBOT before or after CCI resulted in a significant increase in MWT compared to CCI controls. HBOT before CCI resulted in a significant increase in TWL compared to no HBOT. HBOT after CCI resulted in only a 14 d transient increase in TWL compared to CCI control. These results suggest that the antinociceptive effects of HBOT are more substantial when HBOT is given prior to the injury, rather than after injury | HBOT groups demonstrated a reduction in nNOS- and iNOS-positive neurons in the spinal cord at 28d compared to control CCI rats |
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| Ding et al., 2018 [24] | Early hyperbaric oxygen effects on neuropathic pain and nitric oxide synthase isoforms in CCI rats | Chronic constrictive injury of the sciatic nerve (CCI) | (i) Mechanical allodynia (MWT)
(ii) Thermal allodynia (TWL) | 2.5 ATA
FiO2 >90%
60 min
5 sessions (POD1-5) | 1.0 ATA
Room air
60 min
5 sessions | Daily MWT and TWL assessments (POD1-14) | HBOT group had significant increase in both MWT and TWL compared to CCI control that was sustained throughout the assessment period | CCI-induced expression of iNOS and nNOS mRNA and protein in the ipsilateral spinal dorsal horn starting 3d after injury. HBOT treatment causes a significant reduction in the increased expression of these mRNAs and proteins |
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| Fu et al., 2017 [25] | Hyperbaric oxygenation alleviates chronic constriction injury- (CCI-) induced neuropathic pain and inhibits GABAergic neuron apoptosis in the spinal cord | Chronic constrictive injury of the sciatic nerve (CCI) | (i) Mechanical allodynia (MWT) | 2.4 ATA
98%FiO2
60 min
14 sessions (POD1-14) | 1.0 ATA
RA
60 min
14 sessions (POD1-14) | MWT assessed on POD #0, 8, and 14 | HBOT treatment caused a significant increase in MWT compared to CCI control rats on POD8 and POD14 | CCI-induced an increase in apoptotic positive neurons, apoptotic GABA-positive neurons, cleaved caspase 3 positive neurons, and cytochrome C positive neurons on POD 8 and 14. HBOT treatment mitigated the increase for these outcomes at both time points. This suggests the beneficial effect of HBOT in CCI-induced neuropathic pain may be due to its inhibitory role in CCI-induced GABAergic neuron apoptosis via suppressing the mitochondrial apoptotic pathways in the spinal cord |
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