•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.
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.
The headaches that accompany certain intracranial pathologies (such as meningitis, subarachnoid haemorrhage and tumour) have been considered to result from mechanical or chemical stimulation of ...pain-sensitive structures of the intracranial meninges. Although the recurrent headache of migraine is of unknown origin and is not accompanied by an identifiable pathology, it shares with intracranial headaches features that suggest an exaggerated intracranial mechanosensitivity (worsening of the pain by coughing, breath-holding or sudden head movement). One possible basis for such symptoms would be a sensitization of meningeal afferents to mechanical stimuli. Previous studies of neuronal responses to meningeal stimulation have focused primarily on cells in the central portion of the trigeminal pathway, and have not investigated the possible occurrence of sensitization. We have recorded the activity of primary afferent neurons in the rat trigeminal ganglion that innervate the dural venous sinuses. Chemical stimulation of their dural receptive fields with inflammatory mediators both directly excited the neurons and enhanced their mechanical sensitivity, such that they were strongly activated by mechanical stimuli that initially had evoked little or no response. These properties of meningeal afferents (chemosensitivity and sensitization) may contribute to the intracranial mechanical hypersensitivity that is characteristic of some types of clinically occurring headaches, and may also contribute to the throbbing pain of migraine.
CONTEXT.— Adolescents are at highest risk for infection with Chlamydia trachomatis, an important preventable cause of pelvic inflammatory
disease and subsequent tubal factor infertility in US women. ...Current guidelines
for delivery of adolescent primary care services recommend yearly chlamydia
screening for those adolescent females considered to be at risk. OBJECTIVES.— To describe the epidemiology of prevalent and incident chlamydia infection
among adolescent females to assess the appropriate interval for chlamydia
screening and to define risk factors that would identify adolescent females
to target for screening. DESIGN.— Prospective longitudinal study. PATIENTS.— A consecutive sample of 3202 sexually active females 12 through 19 years
old making 5360 patient visits over a 33-month period, January 1994 through
September 1996. SETTING.— Baltimore, Md, family planning, sexually transmitted disease, and school-based
clinics. INTERVENTION.— Testing for C trachomatis by polymerase chain
reaction. MAIN OUTCOME MEASURES.— Prevalence and incidence of C trachomatis infections;
predictors of positive test result for C trachomatis. RESULTS.— Chlamydia infection was found in 771 first visits (24.1%) and 299 repeat
visits (13.9%); 933 adolescent females (29.1%) had at least 1 positive test
result. Females who were 14 years old had the highest age-specific chlamydia
prevalence rate (63 27.5% of 229 cases; P=.01).
The chlamydia incidence rate was 28.0 cases per 1000 person-months (95% confidence
interval, 24.9-31.5 cases). The median time was 7.2 months to a first positive
chlamydia test result and 6.3 months to a repeat positive test result among
those with repeat visits. Independent predictors of chlamydia infection—reason
for clinic visit, clinic type, prior sexually transmitted diseases, multiple
or new partners, or inconsistent condom use—failed to identify a subset
of adolescent females with the majority of infections. CONCLUSIONS.— A high prevalence and incidence of C trachomatis
infection were found among adolescent females. We, therefore, recommend screening
all sexually active adolescent females for chlamydia infection every 6 months,
regardless of symptoms, prior infections, condom use, or multiple partner
risks.
Rami Burstein 1 , 2 , 3 ,
Hiroyoshi Yamamura 1 ,
Amy Malick 2 , 3 , and
Andrew M. Strassman 1
1 Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center; 2 Department of ...Neurobiology and 3 Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115
Burstein, Rami, Hiroyoshi Yamamura, Amy Malick, and Andrew M. Strassman. Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J. Neurophysiol. 79: 964-982, 1998. Chemical activation and sensitization of trigeminal primary afferent neurons innervating the intracranial meninges have been postulated as possible causes of certain headaches. This sensitization, however, cannot explain the extracranial hypersensitivity that often accompanies headache. The goal of this study was to test the hypothesis that chemical activation and sensitization of meningeal sensory neurons can lead to activation and sensitization of central trigeminal neurons that receive convergent input from the dura and skin. This hypothesis was investigated by recording changes in the responsiveness of 23 16 wide-dynamic range (WDR), 5 high threshold (HT), and 2 low threshold (LT) dura-sensitive neurons in nucleus caudalis to mechanical stimulation of their dural receptive fields and to mechanical and thermal stimulation of their cutaneous receptive fields after local application of inflammatory mediators or acidic agents to the dura. Responses to brief chemical stimulation were recorded in 70% of the neurons; most were short, lasting the duration of the stimulus only. Twenty minutes after chemical stimulation of the dura, the following changes occurred: 1 ) 95% of the neurons showed significant increases in sensitivity to mechanical indentation of the dura: their thresholds to dural indentation changed from 1.57 to 0.49 g (means, P < 0.0001), and the response magnitude to identical stimuli increased by two- to fourfold; 2 ) 80% of the neurons showed significant increases in cutaneous mechanosensitivity: their responses to brush and pressure increased 2.5- ( P < 0.05) and 1.6-fold ( P < 0.05), respectively; 3 ) 75% of the neurons showed a significant increase in cutaneous thermosensitivity: their thresholds to slow heating of the skin changed from 43.7 ± 0.7 to 40.3 ± 0.7°C ( P < 0.005) and to slow cooling from 23.7 ± 3.3 to 29.2 ± 1.8°C ( P < 0.05); 4 ) dural receptive fields expanded within 30 min and cutaneous receptive fields within 2-4 h; and 5 ) ongoing activity developed in WDR and HT but not in LT neurons. Application of lidocaine to the dura abolished the response to dural stimulation but had minimal effect on the increased responses to cutaneous stimulation (suggesting involvement of a central mechanism in maintaining the sensitized state). Antidromic activation (current of <30 µA) of dura-sensitive neurons revealed projections to the hypothalamus, thalamus, and midbrain. These findings suggest that chemical activation and sensitization of dura-sensitive peripheral nociceptors could lead to enhanced responses in central neurons and that this central sensitization therefore could result in extracranial tenderness (mechanical and thermal allodynia) in the absence of extracranial pathology. The projection targets of these neurons suggest a possible role in mediating the autonomic, endocrine, and affective symptoms that accompany headaches.
Cutaneous allodynia is common in migraine. In the majority of previous studies on allodynia in migraine, only patients with episodic migraine (EM) were included. Little is known on patterns of ...allodynia in chronic migraine (CM). Since the presence of allodynia is associated with a poor response to triptans, a clinically practical method to test migraine patients for allodynia would be useful to the clinician. The aim of this study was to assess the prevalence of dynamic mechanical (brush) allodynia (BA) in CM, using a clinically practical method. Eighty-nine CM patients were prospectively recruited. Patients were given a structured questionnaire regarding demographic data and migraine characteristics. Allodynia was tested using a 10 x 10-cm gauze pad to brush various areas of the skin lightly. The prevalence of BA in the entire study population and in different patient subgroups was calculated. BA was present in 42.7% (38/89) of the patients. The presence of allodynia was unrelated to age, disease duration or to the occurrence of an acute headache exacerbation at the time of testing. Allodynia was positively associated with a history of migraine aura. BA was most common in the cephalic area, but was also seen in cervical dermatomes. BA is common in CM and, unlike in EM, is not significantly affected by the occurrence of an acute headache exacerbation. This suggests that central trigeminovascular neurons are chronically sensitized in patients experiencing migraine headache >15 days per month. The testing of BA in the clinical setting is possible using a simple and brief approach. It allows the clinician to determine whether the patient is sensitized, a diagnosis that affects treatment decisions.
Abstract We have previously observed that migraine attacks impervious to triptan therapy were readily terminated by subsequent i.v. administration of the non-steroidal anti-inflammatory drug (NSAID) ...ketorolac. Since such attacks were associated with periorbital allodynia—a symptom of central sensitization—we examined whether infusion of the NSAID naproxen can block sensitization of central trigeminovascular neurons in the medullary dorsal horn, using in vivo single-unit recording in the rat. Topical exposure of the cerebral dura to inflammatory soup (IS) for 5 min resulted in a short-term burst of activity (<8 min) and a long-lasting (>120 min) neuronal hyper-responsiveness to stimulation of the dura and periorbital skin (group 1). Infusion of naproxen (1 mg/kg) 2 h after IS (group 1) brought all measures of neuronal responsiveness back to the baseline values recorded prior to IS, and depressed ongoing spontaneous activity well below baseline. When given preemptively 1 h before IS (group 2), naproxen blocked the short-term burst of activity and every long-term measure of neuronal hyper-responsiveness that was studied in the central neurons. The same preemptive treatment, however, failed to block IS-induced short-term bursts of activity in C-unit meningeal nociceptors (group 3). The results suggest that parenteral administration of naproxen, unlike triptan therapy, can exert direct inhibition over central trigeminovascular neurons in the dorsal horn. Though impractical as a routine migraine therapy, parenteral NSAID administration should be useful as a non-narcotic rescue therapy for migraine in the setting of the emergency department.
Exercise training efficiency depends on the training load, as well as on the athlete’s ability to tolerate it. The aim of the present study was to evaluate the effect of fighting simulation (3 ...fights, 6 min each, 30 min rest between fights) on anabolic (IGF-I, LH, FSH, estradiol, and testosterone) and catabolic hormones (cortisol) in elite, male (
n
= 10) and female (
n
= 10) adolescent (12–17 years) Taekwondo fighters. Blood samples were collected before the first and immediately after the third fight. The fighting simulation practice led to significant (
p
< 0.05) decreases in IGF-I (males −27.1 ± 25.6, females −22.4 ± 36.3 ng/ml), LH (males −0.7 ± 1.2, females −2.3 ± 3.3 U/L), and FSH (males −0.9 ± 0.5, females −1.5 ± 1.1 U/L), and to a significant increase (
p
< 0.05) in cortisol (males 141.9 ± 30.1, females 64.1 ± 30.6 mcg/dL) in both genders. Fighting simulation decreases in testosterone (males −1.9 ± 1.6, females −0.02 ± 0.06 ng/mL), and free androgen index (males −20.1 ± 21.5, females −0.3 ± 0.5) were significant (
p
< 0.05) only in male fighters. Exercise had no significant effect on estradiol, sex-hormone-binding globulins or thyroid function tests. Our data demonstrate that the physiologic and psychologic strain of a Taekwondo fighting simulation day led to a catabolic-type circulating hormonal response.
To estimate the global burden of low back pain (LBP).
LBP was defined as pain in the area on the posterior aspect of the body from the lower margin of the twelfth ribs to the lower glutaeal folds ...with or without pain referred into one or both lower limbs that lasts for at least one day. Systematic reviews were performed of the prevalence, incidence, remission, duration, and mortality risk of LBP. Four levels of severity were identified for LBP with and without leg pain, each with their own disability weights. The disability weights were applied to prevalence values to derive the overall disability of LBP expressed as years lived with disability (YLDs). As there is no mortality from LBP, YLDs are the same as disability-adjusted life years (DALYs).
Out of all 291 conditions studied in the Global Burden of Disease 2010 Study, LBP ranked highest in terms of disability (YLDs), and sixth in terms of overall burden (DALYs). The global point prevalence of LBP was 9.4% (95% CI 9.0 to 9.8). DALYs increased from 58.2 million (M) (95% CI 39.9M to 78.1M) in 1990 to 83.0M (95% CI 56.6M to 111.9M) in 2010. Prevalence and burden increased with age.
LBP causes more global disability than any other condition. With the ageing population, there is an urgent need for further research to better understand LBP across different settings.
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