Reaffirming the link between chronic phantom limb pain and maintained missing hand representation

Abstract

Phantom limb pain (PLP) is commonly considered to be a result of maladaptive brain plasticity. This model proposes that PLP is mainly caused by reorganisation in the primary somatosensory cortex, presumably characterised by functional degradation of the missing hand representation and remapping of other body part representations. In the current study, we replicate our previous results by showing that chronic PLP correlates with maintained representation of the missing hand in the primary sensorimotor missing hand cortex. We asked unilateral upper-limb amputees to move their phantom hand, lips or other body parts and measured the associated neural responses using functional magnetic resonance imaging (fMRI). We confirm that amputees suffering from worse chronic PLP have stronger activity in the primary sensorimotor missing hand cortex while performing phantom hand movements. We find no evidence of lip representation remapping into the missing hand territory, as assessed by measuring activity in the primary sensorimotor missing hand cortex during lip movements. We further show that the correlation between chronic PLP and maintained representation of the missing hand cannot be explained by the experience of chronic non-painful phantom sensations or compensatory usage of the residual arm or an artificial arm (prosthesis). Together, our results reaffirm a likely relationship between persistent peripheral inputs pertaining to the missing hand representation and chronic PLP. Our findings emphasise a need to further study the role of peripheral inputs from the residual nerves to better understand the mechanisms underlying chronic PLP.

Keywords: Amputees; Motor control; Neuroimaging; Neuropathic pain; Plasticity.

Fig. 1

Chronic phantom limb pain relates to maintained cortical phantom hand representation. (A) Activity for controls (top) and amputees (bottom) during non-dominant/phantom hand versus feet movements (respectively). Black outlines define the boundaries of the ‘missing hand ROI₁’. (B) Activity in the primary sensorimotor missing hand cortex (ROI₁) during phantom hand movements did not significantly differ from activity during non-dominant hand movements in two-handed controls (top; see also Figure A.1 for a lack of a significant between-group difference in and around the the primary sensorimotor missing hand cortex in a whole-brain analysis). Horizontal lines represent the group averages. Red diamonds represent the sixteen amputees in the strict replication sample [i.e., the amputees that were not tested in Makin, Scholz, et al. (2013)]. The orange triangles represent the eleven amputees that also participated in Makin, Scholz, et al. (2013). Grey circles represent the two-handed control participants. (C) Amputees suffering worse chronic phantom limb pain activated the missing hand cortex more strongly during phantom hand movements (bottom).