Memory impairment means less pain for mice

Clinical observations have reported that individuals with memory deterioration, like in Alzheimer's disease, display a lesser pain sensibility than patients with no cognitive impairment.

To clarify the link between pain and loss of memory, we studied how memory-impaired mice behave when submitted to hotplate nociceptive tests.

For 5 days (D1-D5), male CD1 mice were injected daily intraperitonealy with saline or scopolamine (s, an anticholinergic drug, 0.2 mg/kg) or ketamine (k, an N-methyl-D-aspartate receptor antagonist (NMDAr), 2.5 mg/kg), at doses leading to memory impairment with no analgesic effect. From D6 to D9, all received saline only. They were placed on the hotplate and removed at the first sign of discomfort, response time being recorded.

From D1 to D5, reaction time decreased significantly in controls only and did not change in mice with scopolamine or ketamine. From D6 to D9, response times decreased (p < 0.05 (s) and p < 0.0001 (k)) to reach the steady state of control animals. At D5, response time was significantly prolonged for scopolamine (p < 0.01) and ketamine (p < 0.05), compared to controls.

These results show that pain sensibility needs the integrity of the central cholinergic and of the NMDA systems, and that mice with memory impairment display a lesser pain sensibility than normal mice. Further research on the complex interactions of receptors and neurotransmitters involved in pain and cognition could assist in gaining a better understanding of pain and analgesia in patients with memory impairment and in demented individuals.