The Lateral and Medial Pain Systems in Alzheimer’s Disease

The lateral and medial pain systems are affected differently in Alzheimer’s disease. Both the primary somatosensory cortex and some thalamic nuclei, which belong to the lateral pain system, are relatively unaffected by the histological changes that characterize Alzheimer’s disease, thus indicating that a preserved sensory-discriminative function should be expected.

By contrast, the intralaminar thalamic nuclei, which represent an important component of the affective/emotional medial pain system, are early and progressively affected by the Alzheimer’s disease-related cellular pathology. Therefore, the emotional-affective function should be expected to be affected, as also suggested by the conspicuous neuronal and synaptic loss in the prefrontal and limbic regions.

As expected from this pattern of degeneration, a dissociation between the sensory-discriminative component of pain, which is processed in the lateral pain system, and the affective-emotional component, which is processed in the medial system, is present.

Benedetti et al. (1999b) tested both pain thresholds and pain tolerance in Alzheimer patients by means of phasic and tonic noxious stimuli. In the first case, electrical stimulation was used, whereas in the second case experimental arm ischemia was studied.

By comparing Alzheimer patients with normal subjects of the same age, no difference was found in stimulus detection and pain thresholds, whereas a clear-cut increase in pain tolerance was present in Alzheimer patients. Furthermore, the severity of the disease was assessed by means of the Mini Mental State Examination test (MMSE) and the spectral analysis of the electroencephalogram.

The authors found a straightforward correlation between MMSE scores and pain tolerance, such that the more severe the cognitive impairment was, the higher was the tolerance to pain. The analysis of the electroencephalographic power spectra indicated that patients with low alpha and high delta peaks showed an increase in pain tolerance to both electrical stimulation and ischemia.

Therefore, whereas the sensory-discriminative component of pain was maintained in Alzheimer patients, pain tolerance was altered and depended on the severity of cognitive impairment.


Benedetti, Fabrizio. Placebo Effects (p. 111). OUP Oxford.

Benedetti F, Vighetti S, Ricco C et al. (1999b). Pain threshold and tolerance in Alzheimer’s disease. Pain, 80, 377-82.

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