IMPAIRED CHRONIC PAIN-LIKE BEHAVIOUR AND DISRUPTION OF OPIOIDERGIC SYSTEM IN TASTPM MODEL OF ALZHEIMER’S DISEASE

Chronic pain conditions, especially osteoarthritis (OA), are as common in individuals with Alzheimer's disease (AD) as in the general elderly population, which results in detrimental impact on patient's quality of life. However, alteration in perception of pain in AD coupled with deteriorating ability to communicate pain sensations often result in under-diagnosis and inappropriate management of pain. Therefore, a better understanding of mechanisms in chronic pain processing in AD is needed. Here we explored alterations in OA pain and effect of analgesics in a transgenic mouse model of AD. Following an intra-articular injection of monosodium-iodoacetate (MIA) into the left knee of AD-mice (TASTPM) and age-and-gender-matched C57BL/6J (controls) were tested for mechanical nociceptive thresholds and weight-bearing for up to day 28. Pharmacological and biochemical assessments were conducted in plasma and spinal cord tissue. MIA-induced OA resulted in hindpaw mechanical hypersensitivity (allodynia), initiating on day 3 (p < 0.001), in TASTPM and controls. However, from 14-28 days, TASTPM displayed partial reversal of allodynia. Naloxone, an opioid antagonist, re-established allodynia in TASTPM (p = 0.029) as observed in WT controls. Morphine, an opioid agonist, induced heightened analgesia in AD-mice (p = 0.041). TASTPM exhibited elevated plasma level of β-endorphin post MIA (p = 0.038 vs. WT) which correlated with the impaired allodynia (R2 = 0.589; p = 0.044). Finally, diminished spinal microglial response was observed in the TASTPM compared to controls. This study indicates disrupted opioidergic system in parallel with reduced excitation in the spinal cord of TASTPM as possible mechanisms underlying impaired chronic pain sensitivity in AD. This work provides basis for re-evaluation of opioid analgesic-use for management of pain in AD.