Pain affects cognition: the role of gabapentin and noradrenergic signaling in the brain   January 1st, 2015

There is strong evidence that patients with chronic pain show decreased cognitive task performance, including decreased sustained selective attention, processing speed and memory. Pain in Motion recently reported on Kelly Ickmans’ PhD findings, showing that in patients with various central sensitization pain disorders (fibromyalgia, chronic whiplash associated disorders, chronic fatigue syndrome), cognitive performance is closely related to physical activity levels and endogenous analgesia. Now researchers from the Wake Forest School of Medicine, U.S.A. have published fascinating work shedding light on the mechanism behind cognitive decline in chronic pain. The site is highly interactive and includes several fun and informative features, including the recently launched ‘faces of physical therapy’ with thoughts and stories from Physical Therapists all over the world. 

Suto et al. report an animal neuropathic pain study explaining why gabapentin, an antiepileptic drug often used for the treatment of acute postsurgical and chronic neuropathic pain, results in cognitive side effects. More specifically, they studied the interaction between gabapentin and noradrenergic signaling the rat’s brain. 

The prefrontal cortex is crucial for cognitive performance. The locus coeruleus releases noradrenaline to the prefrontal cortex, which under normal conditions (i.e. moderate levels of noradrenaline are released) strengthens prefrontal cortex functioning. Under conditions of stress, larger amounts of noradrenaline are released and this is typically detrimental to prefrontal functioning. Thus, chronic pain patients might reduce their ability to perform cognitive tasks unconsciously because they are stressed by having to cope with pain. 

What has this got to do with gabapentin? Well, gabapentin activates descending noradrenergic pathways to inhibit pain. Gabapentin activates noradrenergic neurons in the locus coeruleus. This new study by Suto et al. showed that a single administration of gabapentin increases noradrenergic tone in the rat’s prefrontal cortex and impairs attentional processes, possibly explaining why patients receiving gabapentin for acute postsurgical pain will experience cognitive side effects. However, the neuropathic pain model did not reveal a similar effect (i.e. cognition was not affected by gabapentin in neuropathic pain). This observation triggered the authors to speculate that the cognitive side effects of gabapentin are more severe when administered to acute (postoperative) pain patients than to chronic neuropathic pain patients. 


Further reading:

Jo Nijs 

2015 Pain in motion