Higher Functioning Endogenous Opioid System Predicts Better Treatment Response For Neuropathic Pain Treated With Topical NSAIDs: Study

Not only are neuropathic pain symptoms quite common in knee osteoarthritis (OA), but scientists can predict who will respond to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) by assessing the nervous system’s own capacity to regulate pain, new research suggests.  Patients whose tests had indicated superior conditioned pain modulation (CPM) had less pain and fewer neuropathic symptoms at study’s end, in results reported in a scientific poster today at the 30th Annual Meeting of the American Academy of Pain Medicine.


“Clinically, these results indicate that neuropathic symptoms are very common in knee OA and that neuropathic processes — such as changes in conditioned modulation — predict who will respond to a common treatment for knee OA,” said Ajay D. Wasan, MD, MSc, the principal investigator, vice chair for Pain Medicine at UPMC, and a visiting professor at the University of Pittsburgh in Pennsylvania.


Furthermore, Dr. Wasan said, “Patients with neuropathic pain symptoms in OA respond equally as well to topical NSAIDs as those who do not have neuropathic pain symptoms.”

Investigators  conducted a 5-week effectiveness study of diclofenac topical gel, an NSAID, in 44 patients with knee OA (i.e., arthritis caused by a breakdown of the lining of the joints). Patients were extensively tested as to genetically and environmentally influenced physical characteristics. Methods included the use of the Neuropathic Pain Questionnaire (NPQ), the Knee Injury and Osteoarthritis Outcome Score (KOOS, a multidimensional pain and functional assessment), an exercise performance task and quantitative sensory testing (QST).

QST uses brief computer-applied painful stimuli as well as sophisticated manually-applied pain sensitivity testing (such as heat, cold, pressure and pinprick) to assess how the nervous system responds to painful stimuli. QST has been used to identify a range of sensory abnormalities in patients with neuropathic pain (Maier et al, Pain 2010;150(3):439-50).


Institutional Review Board approval and written consent were obtained for the study, which was funded by an investigator-initiated grant from Endo Pharmaceuticals (Nasdaq: ENDP). Of 38 subjects who completed the study, 40% had significant neuropathic symptoms, with a mean of 35/100 on a pain scale, that included burning or shooting sensations and sensitivity to touch. Pain sensitivity at baseline, as measured by QST, had modest correlation to symptoms (.4-.50, p < .01). 

After 4 weeks of treatment with diclofenac gel, there was 30% improvement in pain on average and significant response for neuropathic symptoms (p < .01) and improved function (self-rated and measured, p < .01). 

Using CPM, an index of endogenous pain-inhibitory capacity that was calculated from QST measurements, investigators correctly predicted changes in pain intensity and in neuropathic symptoms (p<.05). Subjects with higher CPM at baseline, representing better functioning endogenous pain-inhibitory systems, reported lower pain intensity and neuropathic pain symptoms at the study’s end (p < .05). 


Endogenous pain modulation refers to a nervous system function that can either enhance or inhibit the pain experience. Frequently cited examples of endogenous pain modulation include soldiers who sustained severe battle injuries but experienced little or no pain, and athletes who continue to play through injuries (Ossipov MH, Scientifica (Cairo) 2012;2012:561761).

The variability of the pain experience along with observations that pain can change in the presence of other factors, including past memories, stress, anxiety, distraction or attention, further suggests the presence of endogenous pain modulatory systems. 

Poster 192 – The Responsiveness to Treatment of the Neuropathic Components of Knee Osteoarthritis and the Use of Quantitative Sensory Testing (QST) to Predict Responders and Non-Responders to Diclofenac Gel 

About AAPM 
The American Academy of Pain Medicine is the premier medical association for pain physicians and their treatment teams with over 2,500 members. Now in its 31st year of service, the Academy’s mission is to optimize the health of patients in pain and eliminate pain as a major public health problem by advancing the practice and specialty of pain medicine through education, training, advocacy and research. Information is available on the Academy’s website at  www.painmed.org.

Comments are closed.