In Context
Lifeline Deborah Gustafson is a professor at the State University of New York-Downstate Medical Center, Department of Neurology, Brooklyn, NY, USA. She is also adjunct professor at the University of Gothenburg, Gothenburg, Sweden, and at the Inserm Unit 011, Versailles, France. She trained as a biologist, nutritional scientist, and epidemiologist, with an interest in basic, clinical and population science. Her main research interests are the mechanisms of action associated with adipose tissue in brain health, cognition, and brain diseases of aging, such as Alzheimer’s disease. See Review page 913
What is your greatest achievement? The opportunity to work with and to get to know so many distinguished colleagues and mentors around the world; and, of course, above all, having my son, Maximilian. Who was your most influential teacher? There have been several influential teachers in my life, both academic and non-academic, in science and in the arts; these people have provided me with an unparalleled world view. What is your greatest regret? I was a nerd for a very, very long time… . As I have evolved from nerdiness, I have had more fun, even as a scientist. What is your greatest fear? Missing ‘the golden opportunity’. As a result, I tend to always have just a few too many options open to me, and have often bitten off more than I can chew. What are you currently reading? The Complete Stories of Kafka and Gustav Klimt: The Complete Paintings. Both were gifts from a good friend. What is your worst habit? Procrastination. Sometimes, putting something off until it absolutely must get done (or is past the deadline) is the only way for me to get it done. How would you improve public understanding of research? I am currently involved in creating an open, neutral forum for scientific discourse within the New York Academy of Sciences. It is a challenge, but well worth it. What was the most memorable comment from your school reports? In a organic chemistry exam, we had to synthesize biomolecules on paper. (I loved pushing electrons around.) After coming up with a pretty good formula, the teaching assistant wrote: “I had not thought of that one before.” I have always wondered what I would have created. What one discovery or invention would most improve your life? The technology to enable existence and accomplishments in parallel universes, and the energy to maximise the experience.
872
Focal point A brief history of pain Hyperalgesia, an increased pain induced by noxious stimulation of peripheral tissue, was first described in 1893.1 Two types of hyperalgesia were subsequently characterised: either at the site of injury (primary hyperalgesia) or extending beyond the site of injury (secondary hyperalgesia). However, until publication of the seminal work by Hardy, Wolff, and Goodell in 1950,2 opinion was polarised between those who maintained that hyperalgesia originated in the CNS and those who thought that it originated in the periphery. In a series of about 500 experiments in 23 individuals (many including the authors themselves), Hardy, Wolff, and Goodell showed that primary hyperalgesia was the result of excitation of the local pain endings, whereas secondary hyperalgesia in undamaged tissue was due to central mechanisms within the dorsal horn of the spinal cord. Some 30 years later, based on measures of the excitability of flexor reflexes in rats after a peripheral burn injury, central changes were shown, with a lowering of thresholds and a change in excitability to elicit the flexor reflex. This model provided a frame for understanding, for the first time, why non-noxious stimuli may give rise to pain, in which the periphery drives neurons in the dorsal horn of the spinal cord into a sensitised state.3 Subsequent studies provided more direct and specific evidence for the role of peripheral and central structures in primary and secondary hyperalgesia.4,5 But further research to better classify hyperalgesia (and allodynia, which is neuropathic pain elicited from a non-noxious stimulus) will help researchers characterise the underlying mechanisms and identify potential targets for drug development.6
Troels S Jensen, Nanna B Finnerup 1 2 3 4
5
6
Head H. On disturbances of sensations with specific reference to the pain of visceral disease. Brain 1893; 16: 1–132. Hardy JD, Wolff HG, Goodell H. Experimental evidence on the nature of cutaneous hyperalgesia. J Clin Invest 1950 29: 115–40. Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983; 206: 686–88. Torebjork HE, Lundberg LE, LaMotte RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol 1992; 448: 765–80. LaMotte RH, Lundberg LE, Torebjork HE. Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol 1992; 448: 749–64. Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 2014; 13: 924–35.
www.thelancet.com/neurology Vol 13 September 2014
Lifeline Deborah Gustafson is a professor at the State University of New York-Downstate Medical Center, Department of Neurology, Brooklyn, NY, USA. She is also adjunct professor at the University of Gothenburg, Gothenburg, Sweden, and at the Inserm Unit 011, Versailles, France. She trained as a biologist, nutritional scientist, and epidemiologist, with an interest in basic, clinical and population science. Her main research interests are the mechanisms of action associated with adipose tissue in brain health, cognition, and brain diseases of aging, such as Alzheimer’s disease. See Review page 913
What is your greatest achievement? The opportunity to work with and to get to know so many distinguished colleagues and mentors around the world; and, of course, above all, having my son, Maximilian. Who was your most influential teacher? There have been several influential teachers in my life, both academic and non-academic, in science and in the arts; these people have provided me with an unparalleled world view. What is your greatest regret? I was a nerd for a very, very long time… . As I have evolved from nerdiness, I have had more fun, even as a scientist. What is your greatest fear? Missing ‘the golden opportunity’. As a result, I tend to always have just a few too many options open to me, and have often bitten off more than I can chew. What are you currently reading? The Complete Stories of Kafka and Gustav Klimt: The Complete Paintings. Both were gifts from a good friend. What is your worst habit? Procrastination. Sometimes, putting something off until it absolutely must get done (or is past the deadline) is the only way for me to get it done. How would you improve public understanding of research? I am currently involved in creating an open, neutral forum for scientific discourse within the New York Academy of Sciences. It is a challenge, but well worth it. What was the most memorable comment from your school reports? In a organic chemistry exam, we had to synthesize biomolecules on paper. (I loved pushing electrons around.) After coming up with a pretty good formula, the teaching assistant wrote: “I had not thought of that one before.” I have always wondered what I would have created. What one discovery or invention would most improve your life? The technology to enable existence and accomplishments in parallel universes, and the energy to maximise the experience.
872
Focal point A brief history of pain Hyperalgesia, an increased pain induced by noxious stimulation of peripheral tissue, was first described in 1893.1 Two types of hyperalgesia were subsequently characterised: either at the site of injury (primary hyperalgesia) or extending beyond the site of injury (secondary hyperalgesia). However, until publication of the seminal work by Hardy, Wolff, and Goodell in 1950,2 opinion was polarised between those who maintained that hyperalgesia originated in the CNS and those who thought that it originated in the periphery. In a series of about 500 experiments in 23 individuals (many including the authors themselves), Hardy, Wolff, and Goodell showed that primary hyperalgesia was the result of excitation of the local pain endings, whereas secondary hyperalgesia in undamaged tissue was due to central mechanisms within the dorsal horn of the spinal cord. Some 30 years later, based on measures of the excitability of flexor reflexes in rats after a peripheral burn injury, central changes were shown, with a lowering of thresholds and a change in excitability to elicit the flexor reflex. This model provided a frame for understanding, for the first time, why non-noxious stimuli may give rise to pain, in which the periphery drives neurons in the dorsal horn of the spinal cord into a sensitised state.3 Subsequent studies provided more direct and specific evidence for the role of peripheral and central structures in primary and secondary hyperalgesia.4,5 But further research to better classify hyperalgesia (and allodynia, which is neuropathic pain elicited from a non-noxious stimulus) will help researchers characterise the underlying mechanisms and identify potential targets for drug development.6
Troels S Jensen, Nanna B Finnerup 1 2 3 4
5
6
Head H. On disturbances of sensations with specific reference to the pain of visceral disease. Brain 1893; 16: 1–132. Hardy JD, Wolff HG, Goodell H. Experimental evidence on the nature of cutaneous hyperalgesia. J Clin Invest 1950 29: 115–40. Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983; 206: 686–88. Torebjork HE, Lundberg LE, LaMotte RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol 1992; 448: 765–80. LaMotte RH, Lundberg LE, Torebjork HE. Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol 1992; 448: 749–64. Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 2014; 13: 924–35.
www.thelancet.com/neurology Vol 13 September 2014
