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      Biological and behavioral markers of pain following nerve injury in humans

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          Highlights

          • •

            Integrating genetic analyses, clinical testing and MRI (PNS/CNS).

          • •

            Early stages of pain development in a group with confirmed neuropathic pain.

          • •

            MRI changes in peripheral nerve fibers resulting from ankle sprain.

          Abstract

          The evolution of peripheral and central changes following a peripheral nerve injury imply the onset of afferent signals that affect the brain. Changes to inflammatory processes may contribute to peripheral and central alterations such as altered psychological state and are not well characterized in humans. We focused on four elements that change peripheral and central nervous systems following ankle injury in 24 adolescent patients and 12 age-sex matched controls. Findings include (a) Changes in tibial, fibular, and sciatic nerve divisions consistent with neurodegeneration; (b) Changes within the primary motor and somatosensory areas as well as higher order brain regions implicated in pain processing; (c) Increased expression of fear of pain and pain reporting; and (d) Significant changes in cytokine profiles relating to neuroinflammatory signaling pathways. Findings address how changes resulting from peripheral nerve injury may develop into chronic neuropathic pain through changes in the peripheral and central nervous system.

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          Most cited references60

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          A self-report measure of pubertal status: Reliability, validity, and initial norms.

          A Petersen, L. Crockett, M. Richards … (1988)
          Puberty is a central process in the complex set of changes that constitutes the transition from childhood to adolescence. Research on the role of pubertal change in this transition has been impeded by the difficulty of assessing puberty in ways acceptable to young adolescents and others involved. Addressing this problem, this paper describes and presents norms for a selfreport measure of pubertal status. The measure was used twice annually over a period of three years in a longitudinal study of 335 young adolescent boys and girls. Data on a longitudinal subsample of 253 subjects are reported. The scale shows good reliability, as indicated by coefficient alpha. In addition, several sources of data suggest that these reports are valid. The availability of such a measure is important for studies, such as those based in schools, in which more direct measures of puberty may not be possible.
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            Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits.

            Javeria A Hashmi, Marwan N Baliki, Lejian Huang … (2013)
            Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain.
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              The epidemiology of ankle sprains in the United States.

              Brian R Waterman, Brett D. Owens, Shaunette Davey … (2010)
              Ankle sprain has been studied in athletic cohorts, but little is known of its epidemiology in the general population. A longitudinal, prospective epidemiological database was used to determine the incidence and demographic risk factors for ankle sprains presenting to emergency departments in the United States. It was our hypothesis that ankle sprain is influenced by sex, race, age, and involvement in athletics. The National Electronic Injury Surveillance System (NEISS) was queried for all ankle sprain injuries presenting to emergency departments between 2002 and 2006. Incidence rate ratios were then calculated with respect to age, sex, and race. During the study period, an estimated 3,140,132 ankle sprains occurred among an at-risk population of 1,461,379,599 person-years for an incidence rate of 2.15 per 1000 person-years in the United States. The peak incidence of ankle sprain occurred between fifteen and nineteen years of age (7.2 per 1000 person-years). Males, compared with females, did not demonstrate an overall increased incidence rate ratio for ankle sprain (incidence rate ratio, 1.04; 95% confidence interval, 1.00 to 1.09). However, males between fifteen and twenty-four years old had a substantially higher incidence of ankle sprain than their female counterparts (incidence rate ratio, 1.53; 95% confidence interval, 1.41 to 1.66), whereas females over thirty years old had a higher incidence compared with their male counterparts (incidence rate ratio, 2.03; 95% confidence interval, 1.65 to 2.65). Compared with the Hispanic race, the black and white races were associated with substantially higher rates of ankle sprain (incidence rate ratio, 3.55 [95% confidence interval, 1.01 to 6.09] and 2.49 [95% confidence interval, 1.01 to 3.97], respectively). Nearly half of all ankle sprains (49.3%) occurred during athletic activity, with basketball (41.1%), football (9.3%), and soccer (7.9%) being associated with the highest percentage of ankle sprains during athletics. An age of ten to nineteen years old is associated with higher rates of ankle sprain. Males between fifteen and twenty-four years old have higher rates of ankle sprain than their female counterparts, whereas females over thirty years old have higher rates than their male counterparts. Half of all ankle sprains occur during athletic activity.
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                Author and article information

                Contributors
                S.A. Holmes
                Journal
                Journal ID (nlm-ta): Neurobiol Pain
                Journal ID (iso-abbrev): Neurobiol Pain
                Title: Neurobiology of Pain
                Publisher: Elsevier
                ISSN (Electronic): 2452-073X
                Publication date PMC-release: 04 December 2019
                Publication date Collection: Jan-Jul 2020
                Publication date (Electronic): 04 December 2019
                Volume: 7
                Electronic Location Identifier: 100038
                Affiliations
                [a ]Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children’s Hospital, Boston, MA 02215, United States
                [b ]Department of Anesthesia, Harvard Medical School, Boston, MA 02115, United States
                [c ]Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305, United States
                [d ]Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands
                [e ]Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands
                [f ]Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, United States
                [g ]Bioinformatic and Systems Biology Center, Beth Israel Deaconess Medical Center, United States
                [h ]Department of Medicine, Harvard Medical School, United States
                Author notes
                [* ]Corresponding author at: Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children’s Hospital, Boston, MA 02215, United States. scott.holmes@ 123456childrens.harvard.edu
                [1]

                Holmes SA and Barakat N are co-first authors.

                Article
                Publisher ID: S2452-073X(19)30013-3 Publisher ID: 100038
                DOI: 10.1016/j.ynpai.2019.100038
                PMC ID: 6926375
                PubMed ID: 31890990
                SO-VID: 01b5cf85-372d-40bf-8bb3-3365c43f790e
                Copyright © © 2019 Published by Elsevier Inc.
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 10 October 2019
                Date revision received : 12 November 2019
                Date accepted : 19 November 2019
                Categories
                Subject: Original Research Article

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