Measuring Peripheral Tissue Activation in Patients with Chronic Pain

There are few objective diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder (WAD), for which objective signs of persistent injuries to the neck are usually lacking.  We sought to visualize painful processes in the neck region by means Positron Emission Tomography (PET) using the tracer C11D-deprenyl, a potential marker for inflammation. Twenty-two patients with chronic pain after a rear impact car accident (WAD grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spinous process of the second cervical vertebra. This suggests that also chronic whiplash patients, in contrast to current paradigms, have signs of persistent localized peripheral tissue inflammation, which may serve as a diagnostic biomarker (Linnman et al. 2012). In addition, ultrasound detectable changes in vascular dynamics in the neck in chronic WAD patients have been demonstrated (Kalawi et al 2013), further supporting the role of ongoing peripheral mechanisms as potential pain generators.

In another study, patients with acute ankle sprain served as a model of acute and chronic pain.  The aim was to explore if signs inflammation in the painful sites could be visualized and quantified to study the healing process following traumatic injury using PET.  Eight otherwise healthy patients with unilateral ankle sprain were imaged acutely and followed up twice, first a month and then up to over one year after injury.  Acutely D-deprenyl uptake was significantly increased by a factor 10.7 (range 2.9-37.3) in the injured as compared to the intact ankle. Patients with persistent pain showed prolonged deprenyl uptake in the injury sites (Gordh et al. 2014, work in progress). The exact binding site of deprenyl is so far unknown. In patients suffering from pain due to tennis elbow, painful sites in the arm could be visualized by a NK1 antagonist PET marker (Peterson et al. 2013).

In conclusion, our investigations demonstrate that different kinds of painful processes in the body can be objectively visualized and quantified with PET imaging.  This strengthens the patients’ self-report of pain, and adds to the methods used for diagnostic work-up for chronic pain patients. It may also stimulate a shift of focus in pain research, to the importance of peripheral nociceptive input as a generator of chronic pain, most likely acting in concert with central sensitization processes.