The journal of pain : official journal of the American Pain Society
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A single gene deletion causes lack of leptin and obesity in B6.V-Lep(ob) (obese; ob) mice compared with wild-type C57BL/6J (B6) mice. This study compared the phenotype of nociception and supraspinal antinociception in obese and B6 mice by testing 2 hypotheses: (1) microinjection of cholinomimetics or an adenosine receptor agonist, but not morphine, into the pontine reticular formation (PRF) is antinociceptive in B6 but not obese mice, and (2) leptin replacement in obese mice attenuates differences in nociceptive responses between obese and B6 mice. Adult male mice (n = 22) were implanted with microinjection guide tubes aimed for the PRF. The PRF was injected with neostigmine, carbachol, nicotine, N(6)-p-sulfophenyladenosine (SPA), morphine, or saline (control), and latency to paw withdrawal (PWL) from a thermal stimulus was recorded. B6 and ob mice did not differ in PWL after saline microinjection into the PRF. Neostigmine, carbachol, and SPA caused PWL to increase significantly in B6 but not obese mice. An additional 15 obese mice were implanted with osmotic pumps that delivered leptin for 7 days. Leptin replacement in obese mice restored the analgesic effect of PRF neostigmine to the level displayed by B6 mice. The results show for the first time that leptin significantly alters supraspinal cholinergic antinociception. ⋯ This study specifies a brain region (the pontine reticular formation), cholinergic neurotransmission, and a protein (leptin) modulating thermal nociception. The results are relevant for efforts to understand the association between obesity, disordered sleep, and hyperalgesia.
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Mild knee pain is a common symptom in later life. Despite this fact, there are few data on the impact of it worsening or how individuals alter their appraisals and behavior when it becomes severe. We sought to describe the changes that accompany a substantial deterioration in characteristic knee pain. A nested case-control analysis of existing cohort data identified 57 adults aged over 50 years experiencing progression from mild to severe characteristic pain intensity 18 months later and compared them, before and after this transition, with 228 controls whose knee pain did not progress. Worsening knee pain was accompanied by a marked increase in pain frequency and extent, functional limitation, depressive symptoms, catastrophising, praying and hoping, and use of oral and topical analgesia. Most individuals consulted a general practitioner either during or after this episode. Although relatively rare, substantial deterioration in knee pain has a major impact on those affected. Timely presentation to primary care, addressing potentially unhelpful appraisals and coping strategies, reinforcing core nonpharmacological management, and future research to identify triggering events for substantial deterioration and loss of adequate pain control should be part of an agenda to improve care for this important minority of older adults with knee pain. ⋯ This article describes what happens when the common symptom of mild knee pain in later life becomes significantly worse. The results may help clinicians understand the health impact, changes in patient appraisal and coping, and treatments that typically accompany this change in symptoms.