Clifford J. Woolf

Bio: Clifford J. Woolf is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Dorsal root ganglion & Spinal cord. The author has an hindex of 141, co-authored 509 publications receiving 86164 citations. Previous affiliations of Clifford J. Woolf include University of Melbourne & Partners HealthCare.

Neuronal plasticity: increasing the gain in pain.

Abstract: We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.

Central sensitization: implications for the diagnosis and treatment of pain.

Abstract: Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

The International Classification of Headache Disorders, 3rd edition (beta version)

Abstract: The International Classification of Headache Disorders, 3 edition (beta version), may be reproduced freely for scientific, educational or clinical uses by institutions, societies or individuals. Otherwise, copyright belongs exclusively to the International Headache Society. Reproduction of any part or parts in any manner for commercial uses requires the Society’s permission, which will be granted on payment of a fee. Please contact the publisher at the address below. International Headache Society 2013. Applications for copyright permissions should be submitted to Sage Publications Ltd, 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP, United Kingdom (tel: þ44 (0) 20 7324 8500; fax: þ44 (0) 207 324 8600) (www.sagepub.co.uk). Translations

A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.

Abstract: A peripheral mononeuropathy was produced in adult rats by placing loosely constrictive ligatures around the common sciatic nerve. The postoperative behavior of these rats indicated that hyperalgesia, allodynia and, possibly, spontaneous pain (or dysesthesia) were produced. Hyperalgesic responses to noxious radiant heat were evident on the second postoperative day and lasted for over 2 months. Hyperalgesic responses to chemogenic pain were also present. The presence of allodynia was inferred from the nocifensive responses evoked by standing on an innocuous, chilled metal floor or by innocuous mechanical stimulation, and by the rats' persistence in holding the hind paw in a guarded position. The presence of spontaneous pain was suggested by a suppression of appetite and by the frequent occurrence of apparently spontaneous nocifensive responses. The affected hind paw was abnormally warm or cool in about one-third of the rats. About one-half of the rats developed grossly overgrown claws on the affected side. Experiments with this animal model may advance our understanding of the neural mechanisms of neuropathic pain disorders in humans.

A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.

Abstract: A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.

How do you feel? Interoception: the sense of the physiological condition of the body.

Abstract: As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.

Wound Healing--Aiming for Perfect Skin Regeneration

Abstract: The healing of an adult skin wound is a complex process requiring the collaborative efforts of many different tissues and cell lineages. The behavior of each of the contributing cell types during the phases of proliferation, migration, matrix synthesis, and contraction, as well as the growth factor and matrix signals present at a wound site, are now roughly understood. Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.