Memory impairment means less pain for mice.
BACKGROUND
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.


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Pickering
Gisèle
G
INSERM EMI 9904, Clinical Pharmacology Department, University Hospital, Clermont-Ferrand, France. gisele.pickering@u-clermont1.fr
Chapuy
Eric
E
Eschalier
Alain
A
Dubray
Claude
C
D000818:Animals; D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D006358:Hot Temperature / Q000009:adverse effects; D007649:Ketamine; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D011930:Reaction Time; D012601:Scopolamine
D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D012601:Scopolamine