Articles: hyperalgesia.
-
Previous studies suggest that nocebo effects, sometimes termed "negative placebo effects," can contribute appreciably to a variety of medical symptoms and adverse events in clinical trials and medical care. In this study, using a within-subject design, we combined functional magnetic resonance imaging (fMRI) and an expectation/conditioning manipulation model to investigate the neural substrates of nocebo hyperalgesia using heat pain on the right forearm. ⋯ Functional connectivity analysis of spontaneous resting-state fMRI data from the same cohort of subjects showed a correlation between two seed regions (left frontal operculum and hippocampus) and pain network including bilateral insula, operculum, ACC, and left S1/M1. In conclusion, we found evidence that nocebo hyperalgesia may be predominantly produced through an affective-cognitive pain pathway (medial pain system), and the left hippocampus may play an important role in this process.
-
Randomized Controlled Trial Comparative Study
Effect of morphine and pregabalin compared with diphenhydramine hydrochloride and placebo on hyperalgesia and allodynia induced by intradermal capsaicin in healthy male subjects.
Intradermal (ID) capsaicin injection in humans induces spontaneous pain, flare, primary hyperalgesia, secondary hyperalgesia, and allodynia. Secondary hyperalgesia and allodynia are a reflection of central sensitization. The effect of treatment of single doses of (1) pregabalin, 300 mg single oral dose, and (2) morphine, 10 mg IV, on the area of secondary hyperalgesia induced by ID capsaicin injection was studied by using a randomized, double-blinded, placebo-controlled, 4-period, cross-over design in 20 healthy men. Compared with active placebo diphenhydramine (50 mg oral dose), pregabalin and morphine significantly reduced the area of secondary hyperalgesia over 15 to 240 minutes after capsaicin injection (approximately 25%, P = .002 and approximately 33%, P < .001, respectively). A smaller reduction was observed when pregabalin and morphine were compared with true placebo (approximately 13%, P = .081 and approximately 24%, P = .009, respectively). Diphenhydramine, on the other hand, increased the area of secondary hyperalgesia in comparison with true placebo (approximately 16%, P = .061). The relationship between the baseline area of hyperalgesia and assay sensitivity suggests that establishing minimum entry criteria for the baseline area of hyperalgesia requirement increases the sensitivity of the assay. ⋯ These results suggest that the minimally invasive intradermal capsaicin model, when it is compared with true placebo, can potentially be used for an early assessment of relevant pharmacology of novel analgesic compounds in healthy subjects. This platform may provide a means to rapidly assess new analgesics and enhance dose selection and decision-making during clinical development.
-
Human brain mapping · Dec 2008
Representation of UV-B-induced thermal and mechanical hyperalgesia in the human brain: a functional MRI study.
Surrogate models of pain and hyperalgesia allow the investigation of underlying mechanisms in healthy volunteers. Here, we investigated brain activation patterns during mechanical and heat hyperalgesia in an inflammatory human pain model using functional magnetic resonance imaging. Heat and mechanical hyperalgesia were induced on the right forearm by UV-B application in 14 healthy subjects. ⋯ We conclude that different types of hyperalgesia in a human surrogate model of inflammatory pain produce different brain activation patterns. This is partly due to a differential processing of thermal and mechanical pain and an interaction of sensitization and modality in the caudal portion of the IFC. Finally, the data provide evidence for the existence of a common "sensitization network" consisting of ACC, bilateral anterior insula, and parts of the IFC.
-
Review
Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain.
Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacologic treatment for pain relief. TENS has been used to treat a variety of painful conditions. This review updates the basic and clinical science regarding the use of TENS that has been published in the past 3 years (ie, 2005-2008). ⋯ This review also highlights data from recent randomized, placebo-controlled trials and current systematic reviews. Clinical trials suggest that adequate dosing, particularly intensity, is critical to obtaining pain relief with TENS. Thus, evidence continues to emerge from both basic science and clinical trials supporting the use of TENS for the treatment of a variety of painful conditions while identifying strategies to increase TENS effectiveness.
-
It has been suggested that spinal cord long-term potentiation (LTP) may contribute to hypersensitivity and hyperalgesia. We have investigated if noxious stimulus-induced spinal cord LTP might have a long lasting effect on supraspinal neuronal activity. First, we verified that spinal LTP was induced by electrical high frequency stimuli (HFS) conditioning applied to the sciatic nerve. ⋯ The study demonstrates that PET may be used as an in vivo method to study regional brain metabolic activity between different conditions. It is concluded that noxious sciatic stimuli which induce spinal cord LTP also affect supraspinal metabolic activity. We suggest that these changes might illustrate a supraspinal maladaptive dysfunction involved in pain hypersensitivity and hyperalgesia.