Combined use of pregabalin and memantine in fibromyalgia syndrome treatment: a novel analgesic and neuroprotective strategy?

Abstract

Fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome that is estimated to affect 4-8 million US adults. The exact molecular mechanisms underlying this illness remain unclear, rendering most clinical treatment and management techniques relatively ineffective. It is now known that abnormalities in both nociceptive and central pain processing systems are necessary (but perhaps not sufficient) to condition the onset and maintenance of FMS. These same systemic abnormalities are thought to be responsible for the loss of cephalic gray matter density observed in all FMS patients groups studied to date. The current scope of FMS treatment focuses largely on analgesia and does not clearly address potential neuroprotective strategies. This article proposes a combined treatment of pregabalin and memantine to decrease the pain and rate of gray matter atrophy associated with FMS. This dual-drug therapy targets the voltage-gated calcium ion channel (VGCC) and the N-methyl d-aspartate receptor (NMDAR) (respectively), two primary components of the human nociceptive and pain processing systems.

Figure 1

Proposed calcium ion-dependent molecular mechanisms of FMS. Abbreviations: A, site of action of memantine; B, site of action of pregabalin; NMDAR, N-methyl D-aspartate receptor; OPRM1, mu-opioid receptor; ROS, reactive oxygen species; SP, substance P; VGCC, voltage-gated calcium ion channel.