Acute Pain Meds Boost SCI Recovery

Posted by Sam Maddox in Research News on August 18, 2016 # Research

The very early trauma care of spinal cord injury usually involves a variety of medications for muting pain, or calming bladder spasms, for maintaining blood pressure, or for keeping infections in check. But has anyone ever considered the effect these drugs have on neurological recovery?

Until recently, the answer was no. But a new paper from a European-Canadian collaboration reports that two common pain medications, when given early on, do more than treat pain. These drugs, a pair of powerful anticonvulsants (gabapentin, pregabalin, also known as Neurontin and its cousin, Lyrica) also improve motor function

The paper, Effects of Pain and Pain Management on Motor Recovery of Spinal Cord–Injured Patients, was authored by Armin Curt, a physician at University Hospital Balgrist, Zurich, Switzerland, and John Kramer, a scientist at the School of Kinesiology, University of British Columbia, and a member of ICORD, the International Collaboration on Repair Discoveries.

According to the paper, approximately 60 percent of patients with acute spinal cord injury develop pain days to weeks after injury; often this persists into chronic pain.

From the paper:
To date, the consequences of pain after SCI have been largely examined in terms of interfering with quality of life. However, preclinical studies indicate that pain and management of pain with different classes of medications may also impact neurological outcomes.

I asked Kramer to discuss the finding that anticonvulsants appear to affect recovery:

Spinal cord injury is a tough situation; there is the immediate traumatic event compounded by other injuries to bone, internal injuries, etc. Our question is about the effect of various early treatments on long term neurological outcome. We examined the hypothesis that pain characteristics -- classification and intensity -- as well as pain management, or medications, affect the course of neurological recovery in patients with SCI.

These drugs are being administered within what might be a window of opportunity for potential repair – is there a possibly they are neuroprotective? Indeed, drugs used in acute SCI may be important modifiers of neurological recovery – the problem is that we really have never bothered to look. This is what my lab is currently focused on doing.

Kramer said his team began by asking what factors would predict recovery; in particular, would the presence of neuropathic pain play a role? Might having pain be a good thing? “There are indications that pain is a plastic event, that is, it appears to involve some degree of nerve remodeling. We also know that plasticity is related to recovery.”

Kramer, Curt and their international collaborators looked at a large amount of pain, sensory and motor score data from two sources, the International Standards for the Neurological Classification of SCI (ISNCSCI) and the European Multicentre Study about SCI (EMSCI). They compared baseline outcomes with data from 225 patients at 19 trauma and rehab centers in Europe.

First, regarding whether having pain is an indicator of better recovery, the answer is no. Pain is pain. The presence of pain has no effect on recovery, except to the extent pain could limit full participation in rehabilitation.

From paper:
We found that regardless of how pain classification was modeled, there was no significant effect of pain on the rate of motor recovery.

And about those anticonvulsants, Neurontin and Lyrica?

Individuals who were treated at this early time point with anticonvulsant drugs recovered an average of 7.3 motor points greater over the first year compared with those untreated with anticonvulsants

Importantly, the effect of anticonvulsants persisted.

Neither NSAIDS (over the counter anti-inflammatory drugs such as Advil or aspirin) nor anticonvulsants had any effects on sensory recovery.

From the paper:

The present findings are the first to demonstrate that acute management of neuropathic pain may have beneficial effects over the first year post-injury. Specifically, individuals treated with anticonvulsants demonstrated greater recovery of muscle function compared with individuals not treated with anticonvulsants. Importantly, the effect of anticonvulsants was observed independently of injury related characteristics, such as the injury severity and level of injury, and other pain medications. ... anticonvulsants had a beneficial effect in both the upper and lower extremities. In addition to motor recovery, anticonvulsants significantly reduced maximum pain intensity during the transition from acute to chronic stages.

Based on our findings, we have identified a significant effect (approximately 7 motor points) of acute anticonvulsant treatment on motor scores after SCI. To put this recovery into context, 7 motor points is comparable to that reported in a landmark clinical trial examining the effects of acutely administered methylprednisolone (NASCIS Trial), and a recent observational study demonstrating the efficacy of early surgical intervention.

Seven points, what does that mean? Would that be considered a clinically meaningful change? It might be for a person with a cervical injury, not so much in mid-spine injuries.

What is the mechanism of anticonvulsants in acute SCI? First, they are possibly neuroprotective, by blocking calcium and sodium channels – essential to the electrochemical function of the nervous system. This may limit such secondary injury effects as free radicals, glutamate release or lipid peroxidation. Because this protection may only be available in a narrow time frame (very early after injury, before any medication for nerve pain would normally be prescribed), the Kramer paper suggests “an interesting alternative: nerve sprouting.

... anticonvulsants may affect endogenous neuroplasticity, such as sprouting. Proposed to mediate spontaneous repair in preclinical models of SCI, sprouting is considered a major therapeutic target for the recovery of neurological function. In line with known mechanisms, anticonvulsants may attenuate aberrant plasticity through a reduction in hyperexcitability. While mechanisms are poorly understood, aberrant neuroplasticity and hyperexcitability in the cord have been suggested as potential underlying substrates of neuropathic pain. Similarly, through the attenuation of aberrant plasticity and hyperexcitability, anticonvulsants administered early after SCI in individuals with neuropathic pain may “redirect” or unmask potential for neurological recovery.

Kramer hopes to see more clinical studies on the potential of anticonvulsants for acute SCI. He says his group also wants to look at other drugs in the early treatment of SCI, including opioids (which might be detrimental to recovery), baclofen and anticholinergics (e.g. Ditropan, widely used for bladder management). “The difficulty with our approach is that you never know if it's the medication or the reason someone is getting the medication that explains the change in recovery.”