An individual with Sarmatian-related ancestry in Roman Britain.

In the second century CE the Roman Empire had increasing contact with Sarmatians, nomadic Iranian speakers occupying an area stretching from the Pontic-Caspian steppe to the Carpathian mountains, both in the Caucasus and in the Danubian borders of the empire.1,2,3 In 175 CE, following their defeat in the Marcomannic Wars, emperor Marcus Aurelius drafted Sarmatian cavalry into Roman legions and deployed 5,500 Sarmatian soldiers to Britain, as recorded by contemporary historian Cassius Dio.4,5 Little is known about where the Sarmatian cavalry were stationed, and no individuals connected with this historically attested event have been identified to date, leaving its impact on Britain largely unknown. Here we document Caucasus- and Sarmatian-related ancestry in the whole genome of a Roman-period individual (126-228 calibrated [cal.] CE)-an outlier without traceable ancestry related to local populations in Britain-recovered from a farmstead site in present-day Cambridgeshire, UK. Stable isotopes support a life history of mobility during childhood. Although several scenarios are possible, the historical deployment of Sarmatians to Britain provides a parsimonious explanation for this individual's extraordinary life history. Regardless of the factors behind his migrations, these results highlight how long-range mobility facilitated by the Roman Empire impacted provincial locations outside of urban centers.

Absence of pain with hyperhidrosis: a new syndrome where vascular afferents may mediate cutaneous sensation.

Congenital absence of pain perception is a rare phenotype. Here we report two unrelated adult individuals who have a previously unreported neuropathy consisting of congenital absence of pain with hyperhidrosis (CAPH). Both subjects had normal intelligence and productive lives despite failure to experience pain due to broken bones, severe cold or burns. Functional assessments revealed that both are generally hypesthetic with thresholds greater than two standard deviations above normal for a several of modalities in addition to noxious stimuli. Sweating was 3 to 8-fold greater than normal. Sural nerve biopsy showed that all types of myelinated and unmyelinated fibers were severely reduced. Extensive multi-antibody immunofluorescence analyses were conducted on several skin biopsies from the hands and back of one CAPH subject and two normal subjects. The CAPH subject had all normal types of immunochemically and morphologically distinct sensory and autonomic innervation to the vasculature and sweat glands, including a previously unknown cholinergic arterial innervation. Virtually all other types of normal cutaneous C, Adelta and Abeta-fiber endings were absent. This subject had no mutations in the genes SCN9A, SCN10A, SCN11A, NGFB, TRKA, NRTN and GFRA2. Our findings suggest three hypotheses: (1) that development or maintenance of sensory innervation to cutaneous vasculature and sweat glands may be under separate genetic control from that of all other cutaneous sensory innervation, (2) the latter innervation is preferentially vulnerable to some environmental factor, and (3) vascular and sweat gland afferents may contribute to conscious cutaneous perception.

The effects of unilateral transcutaneous electrical nerve stimulation of the median nerve on bilateral somatosensory thresholds.

Transcutaneous electrical nerve stimulation (TENS) is used to relieve acute and chronic pain. TENS electrodes are applied at the site of pain or in segments related to the pain, although there is limited research to support either approach. This study investigated the effects of unilateral TENS on mechanical and thermal thresholds at ipsilateral and contralateral sites in healthy human participants. Sensory perception thresholds were measured on the ipsilateral and contralateral thenar eminence of 16 volunteers for von Frey filaments, sharpness, warm, cold and heat pain. TENS was administered over the right median nerve for 10 min at 100 pulses per second (pps) and an intensity which elicited mild tingling in the hand. During TENS, ipsilateral threshold was greater than contralateral threshold for all sensory modalities, although differences were less marked for thermal stimuli. TENS effects had disappeared 30 min after TENS had been switched off although there was a tendency for thermal thresholds to remain elevated. We conclude that during stimulation, TENS elevates somatosensory thresholds within the distribution of the stimulated nerve. The rapid and short-lived ipsilateral effect is consistent with findings from animal studies and suggests a central segmental mechanism.

Somatic sensation and the insular-opercular cortex: relationship to central pain.

We report 5 stroke patients with lesions affecting the insula and parietal operculum sparing the postcentral gyrus (somatosensory cortical area SI); 3 had spontaneous central poststroke pain (CPSP) and 2 did not. All were imaged and underwent quantitative sensory threshold tests, though not all modalities were tested in all subjects. Tactile thresholds were unaltered in all. The patients with CPSP exhibited greatly elevated thresholds for mechanical pain (skinfold pinch), sharpness and thermal sensations; the pain-free patients had distinctly lesser elevations of their skinfold pinch and innocuous and noxious thermal thresholds, and no sharpness deficit. It is therefore suggested that, in the case of similar cortical lesions, the presence or absence of spontaneous pain either modifies the thresholds for some innocuous modalities, or that the degree of deficit of some innocuous modalities determines whether or not central pain occurs.

Allodynia in relation to lesion site in central post-stroke pain.

UNLABELLED: Seventy-one percent of 122 patients with central post-stroke pain (CPSP) had allodynia that was tactile-, cold-, or movement-evoked. Site of thalamic (and some infratentorial) lesions as revealed by magnetic resonance imaging (MRI) was correlated in some cases with allodynia type and sensory perception threshold testing (QST). Notably, patients with cold allodynia tend to have more dorsally placed thalamic lesions than those without, and those with movement allodynia more anteriorly placed lesions. Suggestions are made for improved correlation. PERSPECTIVE: Only about half of patients with CPSP have allodynia (pain caused by innocuous stimulation); such stimulation is usually tactile- or cold-evoked or due to activation of stretch receptors (movement). We have found that, in some of our cases, the type of allodynia may depend on lesion location within the thalamus.

Representation of somatosensory modalities in pathways ascending from the spinal anterolateral funiculus to the thalamus demonstrated by lesions in man.

Patients with cordotomies (16), and brainstem (17) or thalamic (30) infarcts, all except cordotomies verified by magnetic resonance imaging (MRI), have been subjected to quantitative sensory perception threshold testing (QST) for touch (von Frey), mechanical pain, sharpness, innocuous warmth and cold, and heat pain in the maximally affected body area and its unaffected contralateral mirror image region. Some patients were tested twice at widely spaced time intervals; no qualitative differences were found. Results show that all modalities are dissociable from one another by lesions at all levels tested, so that there must be separable representation for each of the six modalities tested. In the lower (crossed symptoms and signs), but not the upper (uncrossed symptoms), deficits for all modalities (except for touch) were more marked than at higher levels. At the level of the thalamus, deficits for innocuous and noxious thermal modalities but not for mechanical pain were recorded in the case of lesions of the principal somatosensory relay nucleus (VPL/Vc), while more medial thalamic lesions resulted in deficits for mechanical pain but not for heat pain or innocuous thermal modalities; there is a marked deficit for sharpness caused by lesions at both thalamic sites.

Dynamic mechanical allodynia in neuropathic pain.

Thirty-four patients with various forms of neuropathic pain have been examined with respect to two parameters of dynamic mechanical allodynia: the effect of repetitive stimulation on pain intensity; and refractory period. Pain intensity increased with repetitive stimulation ('windup') in most patients with neuropathic pain of peripheral origin, while it was not observed in patients with central neuropathic pain. While a non-responsive period occurs after tactile allodynic elicitation in patients with trigeminal neuralgia (Kugelberg and Lindblom, 1959), it was not seen in any case of neuropathic pain, including trigeminal neuropathy. The findings have implications for diagnosis, and require pathophysiological elucidation in terms of revealed differences.

Central representation of somatic sensations in the parietal operculum (SII) and insula.

Four subjects with small restricted cerebral cortical infarcts have been examined. One had a lesion confined to the parietal operculum (SII), while in the second the SII lesion also encroached on the posterior insula; in the third subject, both banks of the sylvian fissure and the dorsal insula were involved, while in the fourth the lesion involved the upper bank of the sylvian fissure. In all cases, the postcentral gyrus (SI) was intact. Subjects 1 and 2 had mild spontaneous pain, but subjects 3 and 4 had never had spontaneous pain. In the affected areas, none could feel mechanical (skinfold pinch) pain. The 2 subjects with spontaneous pain could not discriminate sharpness (pinprick), but this was unimpaired in the third and fourth subjects. Warmth, cold, and heat pain were impaired in the 2 subjects with spontaneous pain, but not in those without; however warm-cold difference was greater in the affected regions of all subjects. The possibility must nevertheless be considered that the presence of central pain in some way alters the cortical mechanisms for the perception of thermal stimuli. Certainly, as we had earlier observed, spontaneous pain only occurs when there is interference with thermal sensation. Functional MRI (fMRI) studies following thermal stimulation in subjects 1 and 2 showed these areas, particularly SII, to be concerned with the reception of innocuous and noxious thermal stimuli, mechanical (skinfold pinch) pain and sharpness (pinprick), implying that SI is principally concerned with the reception of low-intensity mechanical stimuli, although it was activated in 1 of our fMRI-studied subjects by innocuous cooling.

Herpes zoster itch: preliminary epidemiologic data.

The best-known complication of shingles (herpes zoster) is postherpetic neuralgia (PHN). PHN is commonly studied to investigate causes of and treatments for neuropathic pain. However, many patients with shingles experience neuropathic itch accompanying, or instead of, pain. Some report severe disabling postherpetic itch (PHI), and though it is rare, some patients injure themselves by scratching itchy skin that has lost protective sensation. To date, there is virtually no mention of PHI in the medical literature; neither epidemiologic, anatomic, physiologic, nor treatment studies. We analyzed 3 independent existing sets of data from 586 adults with shingles or PHN to glean epidemiologic information about pruritus during and after shingles. All data refer to itch localized to shingles-affected areas and initiated by shingles. They indicate that pruritus, usually mild or moderate, commonly accompanies both acute zoster and PHN. There was no significant difference in age between subjects with and without PHI. In one group, but not in another, there was an increased number of women with PHI. Subjects whose shingles affected the head, face, and neck were more likely to experience PHI than those whose shingles affected the torso. These findings indicate a need for research on zoster-associated itch, including prospective studies on frequency, impact, and treatment.

Factors influencing the features of postherpetic neuralgia and outcome when treated with tricyclics.

This paper retrospectively reviews features of postherpetic neuralgia (PHN) in up to 279 personal patients in relation to treatment outcome when treated with tricyclic antidepressants (TCAs). Factors affecting characteristics of PHN: (i) Patients with allodynia (89%) and/or burning pain (56%) have a much higher visual analogue pain intensity score than those without; (ii) Acyclovir (ACV) given for acute shingles (HZ) does not reduce the incidence of subsequent PHN, but reduces the pain intensity in PHN patients with allodynia; (iii) ACV given for acute HZ reduces the incidence of burning pain in subsequent PHN, but not of allodynia; (iv) ACV given for acute HZ reduces the incidence of clinically detectable sensory deficit in subsequent PHN. Factors affecting outcome of TCA-treated PHN: (i) The point in time at which TCA treatment is commenced is by far the most critical factor: started between 3 and 12 months after acute HZ onset, more than two-thirds obtain pain relief (NNT=1.8); between 13 and 24 months, two-fifths (41%) (NNT=3.6); and more than two years, one-third (NNT=8.3). Background and paroxysmal pain disappear earlier and are more susceptible of relief than allodynia. (ii) Twice as many (86%) of PHN patients without allodynia obtain pain relief with TCA treatment than those with (42%); (iii) the use of ACV for acute HZ more than halves the time-to-relief of PHN patients by TCAs; (iv) PHN patients with burning pain are significantly less likely to obtain pain relief with TCAs than those without (p<0.0001).

Poststroke shoulder pain: a prospective study of the association and risk factors in 152 patients from a consecutive cohort of 205 patients presenting with stroke.

BACKGROUND AND PURPOSE: Shoulder pain is known to retard rehabilitation after stroke. Its causes and prognosis are uncertain. This study describes the incidence of poststroke shoulder pain prospectively, in an unselected stroke population in the first 6 months after stroke and identifies risk factors for developing pain. METHODS: 297 patients with possible stroke were screened and stroke diagnosed in 205 cases. The 152 patients entered the study of which 123 patients were assessed up to 6 months. This cohort, with a mean age of 70.6 years, was examined at 2 weeks, 2, 4, and 6 months. A history of shoulder pain, Barthel score, anxiety and depression score were recorded. Full neurological and rheumatological examination was undertaken, using the contralateral side as a control. Pain outcome and stroke outcome was recorded at subsequent visits. RESULTS: 52 (40%) patients developed shoulder pain on the same side of their stroke. There was a strong association between pain and abnormal shoulder joint examination, ipsilateral sensory abnormalities and arm weakness. Shoulder pain had resolved or improved at 6 months in 41 (80%) of the patients with standard current treatment. CONCLUSIONS: Shoulder pain after stroke occurred in 40% of 123 patients surviving, consenting and not too unwell to participate. This included 52 patients of an original cohort of 205 patients presenting with stroke. Eighty percent of patients made a good recovery with standard treatment Patients with sensory and or motor deficits represent at risk sub-groups.

Human "autotomy".

We describe two cases of self-injurious behaviour. One was a man with central post-stroke pain with maximal pain in the tip of the nose, who excavated his ala nasae--in which he subsequently continued to experience phantom pain. The second case a man who, following ophthalmic herpes zoster and possibly mild postherpetic neuralgia. He subsequently scratched his anaesthetic forehead down to the bone, while denying he experienced any pain. We would describe the first case as one of true autotomy; but the second as destruction of an anaesthetic part of the body. The implications for human and animal physiopathology are discussed.

A double-blind trial of naloxone in central post-stroke pain.

Intravenous naloxone has been claimed to produce pain relief in opioid-resistant central post-stroke pain (CPSP, 'thalamic syndrome'). In a double-blind trial, carried out in 20 patients with established CPSP, naloxone (up to 8 mg in 20 ml vehicle) was tested against normal saline; each patient was randomly given naloxone or saline and the other substance 2 or 3 weeks later. VAS and verbal pain scores were obtained immediately before and after naloxone or saline injection, and subjective ratings followed for 2 weeks. Three patients obtained transient pain relief with naloxone, 4 with saline, and another 4 with both. Statistical tests failed to show any influence of giving naloxone first or second. In all cases except one, pain relief had disappeared by the evening of the day on which the test was performed; one case, following naloxone, continued to experience pain relief until the following morning. We therefore conclude that intravenous naloxone is of no value in alleviating the pain of CPSP.