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Opioids for Post-SCI Pain

To date there are few research studies examining opioids in the treatment of SCI pain. There is a substantial body of research investigating the benefits of opioid analgesics in the treatment of non-cancer chronic pain and some of those studies examined the impact of opioids on neuropathic pain. There are no studies employing opioid analgesics in post-SCI pain. Furlan et al. (2006) conducted a meta-analysis of effectiveness and side-effects of opioid analgesics for chronic non-cancer pain. Their meta-analysis found that opioids reduced pain and improved functional outcomes when compared to placebo for both nociceptive and neuropathic pain syndromes. Strong opioids (oxydone and morphine) were significantly superior to naproxen and nortriptyline for pain relief but not functional outcomes. Weak opioids (propylene, tramadol and codeine) did not significantly do better than NSAIDS or tricyclic anti-depressants for either pain relief or functional outcomes (Furlan et al. 2006). The authors found that clinically, only constipation and nausea were significantly more common with opioids. The big concern with opioids is of course addiction or opioid abuse. Unfortunately, as Furlan et al. (2006) notes in their meta-analysis, the existing randomized trials were not designed to evaluate addiction.

Table 29 Opioids for Post-SCI Pain

Author Year

Country
PEDro Score
Research Design
Total Sample Size

MethodsOutcome
Norrbrink & Lundeberg 2009

Sweden

RCT

PEDro=8

N=35

Population: Mean age=51.3 yr; Gender: males=28, females=7; Level of injury: tetraplegia=16, paraplegia=19; Type of pain=neuropathic.

Treatment: Patients were randomized in a 2:1 ratio (tramadol/placebo) and treatment was administered for 4 wk. Both patients and staff were blind to the treatments. Each patient was given 50 mg tramadol or placebo 3x/day. The daily dose was increased by one tab for 5 5 days to a maximum dose of 8 tab.

Outcome Measures: Patient Global Impression of Change; Multidimensional Pain Inventory

1.     Significant differences were seen in between group pain ratings (p<0.05).

2.     Patient Global Impression of Change rating was significantly higher in the tramadol group than the control group.

3.     Significant improvements were seen in ratings of anxiety, global life satisfaction and sleep quality (p<0.05).

4.     No significant changes were seen in pain pleasantness, depression, or on the MPI scales pain interference, perceived life control, affective distress or social support.

Attal et al. 2002

France

RCT

PEDro=10

N=15

Population: SCI: Mean age=54.9 yr; Gender: males=6, females=9; Mean duration of pain=5 yr; Type of pain=neuropathic and nociceptive.

Treatment: Initially, patients received intravenous morphine titrated up to the maximal tolerated dosage using successive bolus injections of 2 mg morphine every 10 minutes. Double blind phase began 3 wk after titration phase.

Outcome Measures: Spontaneous pain, tactile allodynia, psychophysical measurements, mechanical detection and pain thresholds, thermal detection and pain.

1.     Spontaneous pain scores decreased immediately after the end of the infusion of morphine and placebo for up to 120 min in both groups.

2.     The effects of the morphine did not differ significantly from those who were given the placebo post injection.

3.     Those who reported pain relief from the treatment was higher (3x) after the morphine than after the placebo was given from 15-60 min post injection.

4.     Burning pain was weakened by the morphine in seven patients and by placebo in four patients.

5.     When looking at the effects of morphine on mechanical allodynia it could be seen that the morphine produced a reduction in intensity. The saline treatment did not have an effect.

6.     Morphine only significantly reduced dynamic mechanical allodynia (p<0.01).

Eide et al. 1995

Norway

RCT

PEDro=7

N=9

 

Population: Age=25-72 yr; Gender: males=8, females=1; Level of injury: cervical, thoracic; Severity of injury: AIS: A-D; Onset of pain: <6 mo post injury, Length of pain: 14-94 mo; Type of pain=neuropathic.

Treatment: Ketamine hydrochloride, alfentanil or a placebo was given as combination of bolus and continuous intravenous infusions. The bolus dose was administered for 60 sec and the continuous intravenous infusion started simultaneously and was delivered by IVAC syringe pump. This lasted 17-21 min while the testing was performed.

Outcome Measures: Visual Analogue Scale (VAS).

1.     Freidmann’s two-way analysis by ranks showed differences between the various treatments (p=0.005).

2.     The effect of alfentanil and ketamine was also significant (p<0.01 and p<0.04 respectively).

3.     No significant differences were noted between the actions of ketamine and alfentanil (Wilcoxon p=0.19).

4.     Significant differences were noted between the treatment groups (p=0.008). It was also noted that allodynia was not more changed by ketamine than by alfentanil (Wilcoxon p=0.93).

5.     Alfentanil reduced wind-up-like pain (p=0.014) compared to the placebo group. The effect of ketamine on wind-up-like pain was not significantly reduced (p=0.07).

5.     A high correlation between the serum concentration of ketamine and the reduction of continuous pain (r=0.78, p<0.002) and the reduction of wind-up-like pain (r=0.83, p<0.002) was noted.

Barrera-Chacón et al. 2011

Spain

Pre-Post

Nstart=57

Nend=54

Population: Age: 46.4 yr, Severity of injury: AIS A=27, B=1, C=10; Type of pain=neuropathic.

Intervention: Participants were provided with oxycodone treatment for neuropathic pain.

Outcome Measures: Visual Analogue Scale (VAS)

1.     Pain intensity significantly decreased after 3 mo of oxycodone treatment, p<0.001.

2.     Improvement in sleep and physical activity levels was also seen.

3.     83% of individuals were taking adjunct anticonvulsant treatment.

4.     The most common side effect included constipation (33%).

Discussion

Attal et al. (2002) found the intravenous morphine titrated to maximal tolerated dosage, significantly reduced dynamic mechanical allodynia but not necessarily spontaneous or burning pains. Oral opioids remain untested in this population.

Norrbrink and Lundeberg (2009) conducted a double-blind RCT to assess the efficacy of tramadol in 35 SCI individuals diagnosed with at- or below- level neuropathic pain. The authors reported significant differences between the two group pain ratings (p<0.05). Tramadol was also found to be effective in improving anxiety, global life satisfaction and sleep quality in individuals with post SCI pain (p<0.05). However, no significant improvement was seen in pain unpleasantness and depression levels.

Eide et al. (1995) randomly assigned individuals with chronic SCI pain into three groups receiving ketamine hydrochloride, alfentanil (m-opioid receptor agonist) or placebo treatment. The study found alfentanil and ketamine effectively reduced SCI pain compared to placebo treatment (p<0.04, p<0.01); however no difference was seen between the two treatments in overall pain. Alfentanil significantly reduced wind up like pain while ketamine did not.

In a pre-post study, Barrera-Chacón et al. (2010) found oxycodone significantly decreased pain intensity and improved sleep (p<0.001) among individuals experiencing neuropathic pain post SCI. These effects were seen mostly in combination with anticonvulsant treatment.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Attal et al. 2002) that intravenous morphine significantly reduces mechanical allodynia more than placebo.

There is level 1b evidence (from one randomized controlled trial; Norrbrink & Lundeberg 2009) that tramadol is effective in reducing neuropathic pain post SCI.

There is level 1b evidence (from one randomized controlled trial; Eide et al. 1995) that alfentanil reduces overall post SCI pain.

There is level 1b evidence (from one randomized controlled trial; Eide et al. 1995) that alfentanil is more effective at reducing wind up like pain than ketamine.

There is level 4 evidence (from one pre-post study; Barrera-Chacon et al. 2010) that oxycodone and anticonvulsants may be effective in improving SCI neuropathic pain.

Intravenous morphine reduces mechanical allodynia.

Tramadol reduces neuropathic pain.

Alfentanil reduces chronic pain post SCI.

Alfentanil is more effective in reducing wind up like pain post SCI than ketamine.

Oxycodone and anticonvuslants may improve neuropathic SCI pain.