Post-operative
cognitive dysfunction (POCD) is a debilitating clinical phenomenon in elderly patients. Management of
pain in elderly is complicated because
analgesic opiates elicit major side effects. In contrast,
paracetamol (
acetaminophen) has shown
analgesic efficacy, no impact on cognition, and its side effects are well tolerated. We investigated the efficacy of
paracetamol, compared to the
opioid analgesic buprenorphine, in a model of POCD by investigating
cognitive decline,
allodynia, peripheral and hippocampal
cytokines levels, and hippocampal microtubule dynamics as a key modulator of synaptic plasticity. A POCD model was developed in middle-aged (MA) rats by inducing a tibia fracture via orthopaedic surgery. Control MA rats did not undergo any surgery and only received
isoflurane anaesthesia. We demonstrated that
cognitive decline and increased
allodynia following surgery was prevented in
paracetamol-treated animals, but not in animals which were exposed to
anesthesia alone or underwent the surgery and received
buprenorphine. Behavioral alterations were associated with different peripheral
cytokine changes between
buprenorphine and
paracetamol treated animals.
Buprenorphine showed no central effects, while
paracetamol showed modulatory effects on hippocampal
cytokines and markers of microtubule dynamics which were suggestive of neuroprotection. Our data provide the first experimental evidence corroborating the use of
paracetamol as first-choice
analgesic in POCD.