Pain Relief Evident in Type of MRI Scan Could Aid Drug Development

Pain Relief Evident in Type of MRI Scan Could Aid Drug Development

Functional magnetic resonance imaging (FMRI) measures of the brain’s neural response to pain may be a viable tool for evaluating the effectiveness of new pain medications under development, according to the study “Disambiguating Pharmacodynamic Efficacy from Behavior with Neuroimaging,”published in the journal Anesthesiology.

Chronic pain affects 20 percent of the European population, yet effective analgesics are relatively few. Many potential compounds identified in preclinical research fail to reach the market, either discarded after poor results in randomized human trials or due to the difficulties in translating analgesic efficacy in animals to patients. Identifying the potential effectiveness of compounds early would help both by limiting unnecessary human exposure to ineffective compounds and by giving support to difficult but promising medications.

Vishvarani Wanigasekera, PhD, a clinical post-doctoral research fellow at Nuffield Division of Anaesthetics, University of Oxford, and colleagues found that treating pain with analgesics may be measured through the use of FMRI, which could assist in drug development for conditions such as fibromyalgia“We believe that neuroimaging techniques, such as [functional MRI] FMRI, can provide objective evidence that can be used as outcome measures in early drug development to enhance the efficiency of the drug development process,” Dr. Wanigasekera said in a news release.

Researchers conducted a double-blind, randomized Phase I study in 24 healthy people. They assessed the usefulness of FMRI with capsaicin-induced central sensitization, a mechanism relevant in neuropathic pain, to differentiate an effective analgesic (1,200-mg gabapentin) from an ineffective analgesic (600-mg ibuprofen), and both drugs from placebo.

The researchers applied 1 percent capsaicin cream on the anteromedial aspect of each participants’ right lower leg, in a 4 cm area 14 cm above the medial malleolus. Dynamic mechanical allodynia (the experience of pain from a non-painful stimulation of the skin, such as a light touch) and hyperalgesia (an increased sensitivity to pain) were elicited in an area 2 cm below the area treated with capsaicin. Pain was assessed on a visual analogue scale (VAS).

In the absence of behavioral measures distinguishing which drug was most effective at low subject numbers, researchers found that the imaging responses were clear. Pain relevant neural activity was significantly reduced in the subjects who received gabapentin, even with extremely low subject numbers. Although the mechanisms and neural activity involved in pain expression in neuropathic patients is not the same as in healthy subjects with capsaicin cream-induced pain, FMRI has the potential to make a drug’s effect clear in small cohorts, and such studies in early human drug development may determine if a drug can affect relevant neural activity in the brain.

“Many potential pain relieving drugs identified in preclinical research fail to reach the market because of a lack of early objective evidence that shows whether a drug is effectively reaching target pain receptors in the body and regulating chronic pain mechanisms,” Dr. Wanigasekera said. “We have used noninvasive FMRI to successfully obtain such evidence that we hope can help to prevent the premature discarding of potentially effective pain relievers, as well as avoid exposing patients to ineffective ones.”

“There is a clear need for more effective, safer pain relievers,” Dr. Wanigasekera added. “Chronic pain is a very common condition.  Even the most effective pain medications currently available only provide adequate pain relief, defined as a 50 percent reduction in pain, in one out of four patients, while some drugs, such as opioids, have significant side effects, including dependence and overuse.”