The effect of ketamine on inhibitory pain mechanimsm in the central nervous system in chronic pain patients.

The last years research on pain perception has been focusing on central pain modulatory systems like Diffuse Noxious Inhibitory Control (DNIC) and offset analgesia. Dysfunction of DNIC is associated with chronic pain diseases like irritable bowel syndrome and fibromyalgia. Furthermore, accumulating evidence is available about the involvement of the N-methyl-D-aspartate receptor (NMDAR) on chronic pain states. It has recently been shown that the NMDAR-antagonist ketamine can accomplish long-lasting pain relief in patients diagnosed with Complex Regional Pain Syndrome Type-1 (CRPS-1). This study will focus on DNIC and offset analgesia in patients diagnosed with CRPS-1, small-fibre neuropathy and fibromyalgia, compared to healthy controls. The effect of ketamine on pain relief as well as on DNIC and offset analgesia will be investigated.

A total of 60 subjects will be tested for DNIC and offset analgesia. The DNIC experiment is performed by applying a noxious, thermal heat stimulus to the forearm with simultaneous immersion of the subjects foot in cold water. During the test, the subjects records real time pain scores with an Electronically Visual Analogue Scale (eVAS). Offset analgesia is tested by giving a noxious thermal stimulus which is increased with 1°C for 5 sec. Again the subject will real time score the amount of pain using the eVAS. Both experiments will be performed before and after infusion with low-dose (S+)-ketamine.

The main end-point of this study is the effect of ketamine on eVAS, which will be evaluated in a within group comparison using a paired t-test. A separate analysis will be done evaluating the effect of ketamine on DNIC and offset analgesia. For the between group comparison an analysis of variance will be performed comparing the patient groups to the age- and sex matched control group.

In this study it is hypothesised that the inhibitory pain mechanisms DNIC and offset analgesia are affected in chronic pain patients compared to healthy controls. Furthermore it is hypothesised that ketamine has a improving effect on these pain mechanisms.

One trial takes 6 hours. Subjects need to come only ones.

The administration of intravenous S(+)-ketamine.