Abstract
BackgroundChronic 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 the development and progression of OA pain and the effect of analgesics in a transgenic mouse model of AD.MethodsUnilateral OA pain was induced chemically, via an intra‐articular injection of monosodium iodoacetate (MIA) in the left knee joint of AD‐mice (TASTPM) and age‐ and gender‐matched C57BL/6J (WT). Pharmacological and biochemical assessments were conducted in plasma and spinal cord tissue.Results MIA resulted in hind paw mechanical hypersensitivity (allodynia), initiating on day 3, in TASTPM and WT controls. However, from 14 to 28 days, TASTPM displayed partial attenuation of allodynia and diminished spinal microglial response compared to WT controls. Naloxone, an opioid antagonist, re‐established allodynia levels as observed in the WT group. Morphine, an opioid agonist, induced heightened analgesia in AD‐mice whilst gabapentin was devoid of efficacy. TASTPM exhibited elevated plasma level of β‐endorphin post‐MIA which correlated with impaired allodynia.ConclusionsThese results indicate an alteration of the opioidergic system in TASTPM as possible mechanisms underlying impaired persistent pain sensitivity in AD. This work provides basis for re‐evaluation of opioid analgesic use for management of pain in AD.SignificanceThis study shows attenuated pain‐like behaviour in a transgenic mouse model of Alzheimer's disease due to alterations in the opioidergic system and central plasticity mechanisms of persistent pain.
Highlights
Alzheimer’s disease (AD) is the most common cause of dementia (> 60% of dementia) in the elderly population
These results indicate an alteration of the opioidergic system in TASTPM as possible mechanisms underlying impaired persistent pain sensitivity in AD
We observed that mechanical hypersensitivity developed comparably in TASTPM; the AD mice exhibited a partial recovery demonstrated by significantly higher mechanical thresholds than in WT mice from day 21 post monosodium iodoacetate (MIA) injection (Fig. 2A)
Summary
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. Methods: Unilateral OA pain was induced chemically, via an intra-articular injection of monosodium iodoacetate (MIA) in the left knee joint of AD-mice (TASTPM) and ageand-gender-matched C57BL/6J (WT). Results: MIA resulted in hind paw mechanical hypersensitivity (allodynia), initiating on day 3, in TASTPM and WT controls. From 14 to 28 days, TASTPM displayed partial attenuation of allodynia and diminished spinal microglial response compared to WT controls. An opioid antagonist, re-established allodynia levels as observed in the WT group. TASTPM exhibited elevated plasma level of β-endorphin post MIA which correlated with the impaired allodynia. Conclusions: These results indicate an alteration of the opioidergic system in TASTPM as possible mechanisms underlying impaired persistent pain sensitivity in AD. This work provides basis for re-evaluation of opioid analgesic-use for management of pain in AD. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation
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