Peripheral Nerve Trunks Research Articles

A Novel Association Between Resident Tissue Macrophages and Nerves in the Peripheral Stroma of the Murine Cornea

To characterize the interactions between resident macrophage populations and nerves in naïve and injured corneas of the mouse eye. Corneas from wild-type (WT) C57BL/6J, BALB/cJ, and transgenic Cx3cr1-eGFP mice were subjected to a 1-mm central epithelial debridement injury. The eyes were fixed and immunostained as flat mounts with a range of antibodies to identify macrophages, neurons, and Schwann cells. Interactions between nerves and immune cells were analyzed and quantitated using three-dimensional reconstructions of confocal microscopy images. Naïve eyes acted as controls. A distinctive association between resident immune cells and corneal nerves was noted in the peripheral or perilimbal stromal nerve trunks. These epineurial cells were mostly Cx3cr1(+) Iba-1(+) major histocompatibility complex (MHC) class II(+) F4/80(+) CD11b(+) macrophages. The number of nerve-associated macrophages was greater in WT BALB/c mice than in C57BL/6J mice. There were no qualitative or quantitative differences in the circumferential distribution of nerve-associated macrophages in the cornea. Sterile corneal epithelial debridement led to a dissociation of macrophages from peripheral nerve trunks as early as 2 hours postinjury, with numbers returning to baseline after 72 hours. This dissociation was Cx3cr1 dependent. This study is the first to highlight a direct physical association between nerves and resident immune cells in the murine cornea. Furthermore, we reveal that this association in normal eyes is responsive to central corneal epithelial injury and is partly mediated by Cx3cr1 signaling. This association may serve as an indicator of malfunctioning neuroimmune communication in disease states such as neurotrophic keratitis and peripheral neuropathy.

Pancytopenia due to lepromatous involvement of the bone marrow: Successful treatment with multidrug therapy

Leprosy is a chronic infectious disease with a wide spectrum of signs and symptoms depending on the ability of the host's immune system to resist the infection. The disease is frequently associated with sensory loss in skin lesions and damage in peripheral nerve trunks leading to nerve function impairment. In lepromatous leprosy, the immune system offers no protection against the multiplying bacilli and this results in heavy infiltration of the internal organs. We report a case of florid lepromatous leprosy with bone marrow suppression due to the disease, presenting with anemia, leukocytopenia and thrombocytopenia. The hematological abnormalities were fully reversed by mutidrug therapy for leprosy. We suggest that infiltration of the bone marrow by Mycobacterium leprae can cause pancytopenia, which can be cured by treatment of the leprosy alone.

Use of Distribution of F-Latency (DFL) in the Detection of Cervical Spondylotic Neuropathy

Distribution of F-latencies (DFL) is a new nerve conduction parameter introduced by our laboratory to give a distribution of the conduction velocity (DCV) of motor nerve fibres in a peripheral nerve trunk simply as its mirror image. Earlier work revealed an association between Cervical Spondylotic (CS) neuropathy and DFL patterns obtained from the thenar muscle at the base of the thumb by artificially stimulating the median nerve. DFL froom normal subjects had a single peaked pattern, while that from subjects with CS had double or triple peaks, or a broad peak. The broad peak was suggested to be an indicator of early CS, even when the symptoms are not fully apparent. This led to some hypotheses based on physics, physiology and statistics, in order to explain such patterns. In order to verify these hypotheses, experiments need to be carried out carefully, and the present work is a step towards that goal. In this work DFL of the median nerve was obtained from 15 subjects, 6 normal, and 9 with diagnosed cervical spondylosis. The latter were subjected to further X-ray and MRI investigations, performed blindly at regular clinics. All of the 9 subjects were identified with either compression of nerve roots (radiculopathy), or spinal cord compression due to the bulging of the inter-vertebral discs (myelopathy). This shows with confidence that double or triple peaks of DFL indeed relates to CS, and broad peaks indicate their early stage. The same concept may be extended to other peripheral nerves, both in the hands and legs. Thus DFL may become an important screening test for neuropathy, as a first choice, offering a low cost and widely available test compared to the only other alternative, MRI, for such diagnosis. DOI: http://dx.doi.org/10.3329/bjmp.v4i1.14676 Bangladesh Journal of Medical Physics Vol.4 No.1 2011 37-42

Giant Sporadic Low Grade Malignant Peripheral Nerve Sheath (MPNST) of Left Thigh

Malignant Peripheral Nerve Sheath Tumours (MPNST) are rare spindle- cell sarcomas which are derived from the schwann cells or the pleuripotent cells of the neural crest. MPNSTs are usually located in the peripheral nerve trunk roots, extremities and in the head and neck region. These tumours may arise as sporadic variants or in patients with neurofibromatosis1 (NF1). The estimated incidence of MPNSTs in the patients with NF1is 2-5% as compared to a 0.001% incidence in the general population. Herein, we are reporting a case of a giant sporadic (NF1 independent) low grade MPNST of the left thigh in 65 year female patient, which had a good prognosis.

High-Frequency Transcutaneous Peripheral Nerve Stimulation Induces a Higher Increase of Heat Pain Threshold in the Cutaneous Area of the Stimulated Nerve When Confronted to the Neighbouring Areas

Background. TENS (transcutaneous electrical nerve stimulation) is probably the most diffused physical therapy used for antalgic purposes. Although it continues to be used by trial and error, correct targeting of paresthesias evoked by the electrical stimulation on the painful area is diffusely considered very important for pain relief. Aim. To investigate if TENS antalgic effect is higher in the cutaneous area of the stimulated nerve when confronted to neighbouring areas. Methods. 10 volunteers (4 males, 6 females) underwent three different sessions: in two, heat pain thresholds (HPTs) were measured on the dorsal hand skin before, during and after electrical stimulation (100 Hz, 0.1 msec) of superficial radial nerve; in the third session HPTs, were measured without any stimulation. Results. Radial nerve stimulation induced an increase of HPT significantly higher in its cutaneous territory when confronted to the neighbouring ulnar nerve territory, and antalgic effect persisted beyond the stimulation time. Conclusions. The location of TENS electrodes is crucial for obtaining the strongest pain relief, and peripheral nerve trunk stimulation is advised whenever possible. Moreover, the present study indicates that continuous stimulation could be unnecessary, suggesting a strategy for avoiding the well-known tolerance-like effect of prolonged TENS application.

Ultrasound assessment on selected peripheral nerve pathologies. Part I: Entrapment neuropathies of the upper limb - excluding carpal tunnel syndrome.

Ultrasound (US) is one of the methods for imaging entrapment neuropathies, post-traumatic changes to nerves, nerve tumors and postoperative complications to nerves. This type of examination is becoming more and more popular, not only for economic reasons, but also due to its value in making accurate diagnosis. It provides a very precise assessment of peripheral nerve trunk pathology – both in terms of morphology and localization. During examination there are several options available to the specialist: the making of a dynamic assessment, observation of pain radiation through the application of precise palpation and the comparison of resultant images with the contra lateral limb. Entrapment neuropathies of the upper limb are discussed in this study, with the omission of median nerve neuropathy at the level of the carpal canal, as extensive literature on this subject exists. The following pathologies are presented: pronator teres muscle syndrome, anterior interosseus nerve neuropathy, ulnar nerve groove syndrome and cubital tunnel syndrome, Guyon's canal syndrome, radial nerve neuropathy, posterior interosseous nerve neuropathy, Wartenberg's disease, suprascapular nerve neuropathy and thoracic outlet syndrome. Peripheral nerve examination technique has been presented in previous articles presenting information about peripheral nerve anatomy [Journal of Ultrasonography 2012; 12 (49): 120–163 – Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the example of the median nerve; Part II: Peripheral nerves of the upper limb; Part III: Peripheral nerves of the lower limb]. In this article potential compression sites of particular nerves are discussed, taking into account pathomechanisms of damage, including predisposing anatomical variants (accessory muscles). The parameters of ultrasound assessment have been established – echogenicity and echostructure, thickness (edema and related increase in the cross sectional area of the nerve trunk), vascularization and the reciprocal relationship with adjacent tissue.

Differential, size-dependent sensory neuron involvement in the painful and ataxic forms of primary Sjögren's syndrome-associated neuropathy

Primary Sjögren's syndrome (pSS)-associated neuropathy manifests a wide variety of peripheral neuropathies that may show overlap among the neuropathic forms. In this report, we describe histopathological findings of two autopsy cases with pSS-associated neuropathy; one of them manifested the painful form and another showed ataxic form. The population of dorsal root ganglion (DRG) neurons and the density of myelinated fibers in the dorsal spinal root were variably reduced among spinal segments in both forms. In the painful form, there was a prominent reduction of small neurons, while in the ataxic form, large neurons were predominately lost. In accordance with the degree of the DRG cell loss, the modality of nerve fiber loss in the dorsal spinal roots and sural nerve correlated well with the corresponding DRG neuron loss. Prominent CD8+ T lymphocyte infiltration was present in the DRG, sympathetic ganglion, epineurial and perineurial space throughout the peripheral nerve trunks, and visceral organs, including the submandibular gland of both forms.Although the size of affected DRG neurons is different, these two forms share a similar causal mechanism, namely, cytotoxic autoimmunity to ganglion neurons, which may be one of a continuum of etiological factors. This hypothesis may have an impact on therapeutic approach.

Nerve damage in leprosy: a continuing challenge to scientists, clinicians and service providers

This review focuses on nerve damage in leprosy. We present evidence to support the argument that leprosy is best seen as a chronic neurological condition rather than a simple skin disease. Nerve damage affects small dermal nerves and peripheral nerve trunks. Perineural inflammation is a characteristic and hallmark of early leprosy. T cell-mediated inflammation is the main pathological process in leprosy nerve damage. The level of nerve damage in leprosy is high with up to 60% of multibacillary patients having clinically apparent nerve damage at the time of diagnosis; 30% of patents may develop further nerve damage during treatment and 10% may develop new nerve damage after drug treatment. Since the nerve damage is immune mediated, the antibiotics used to treat Mycobacterium leprae infection have little effect on the accompanying nerve damage. This requires treatment with immunosuppressants to stop the inflammation. Treatment of nerve damage with steroids can be effective but about 50% of patients relapse and require a further course of steroids. Research is needed to refine steroid regimens to be used and define appropriate alternatives. Neuropathic pain is now being recognised as another late complication for leprosy patients. There are also service challenges relating to how best to identify patients who need steroid treatment and how to manage patients with established neuropathy who may require health services for many years.

Behavioral and Molecular Exploration of the AR-CMT2A Mouse Model Lmna R298C/R298C

In 2002, we identified LMNA as the first gene responsible for an autosomal recessive axonal form of Charcot-Marie-Tooth disease, AR-CMT2A. All patients were found to be homozygous for the same mutation in the LMNA gene, p.Arg298Cys. In order to investigate the physiopathological mechanisms underlying AR-CMT2A, we have generated a knock-in mouse model for the Lmna p.Arg298Cys mutation. We have explored these mice through an exhaustive series of behavioral tests and histopathological analyses, but were not able to find any peripheral nerve phenotype, even at 18 months of age. Interestingly at the molecular level, however, we detect a downregulation of the Lmna gene in all tissues tested from the homozygous knock-in mouse Lmna (R298C/R298C) (skeletal muscle, heart, peripheral nerve, spinal cord and cerebral trunk). Importantly, we further reveal a significant upregulation of Pmp22, specifically in the sciatic nerves of Lmna (R298C/R298C) mice. These results indicate that, despite the absence of a perceptible phenotype, abnormalities exist in the peripheral nerves of Lmna (R298C/R298C) mice that are absent from other tissues. Although the mechanisms leading to deregulation of Pmp22 in Lmna (R298C/R298C) mice are still unclear, our results support a relation between Lmna and Pmp22 and constitute a first step toward understanding AR-CMT2A physiopathology.

Identification of Motor and Sensory Fascicles in Peripheral Nerve Trunk Using Immunohistochemistry and Micro-Raman Spectroscopy

To explore a time-efficient method of identifying motor and sensory fascicles in peripheral nerve trunk. Thirty Wistar rats were selected to obtain whole spine. The spinal dorsal roots and ventral roots, and sciatic nerve were harvested as sensor, motor, and mixed samples, annexin V and agrin specificities were observed with Western blot and immunohistochemistry. A total of 32 New Zealand rabbits were selected and killed. The roots of spinal nerves were exposed under an operating microscope, and the ventral and dorsal roots, ∼3 mm to 5 mm, were dissociated, and frozen as transverse sections of 30-μm thickness. The sections were examined by micro-Raman spectroscopy. The annexin V and agrin were special substances of sensory and motor nerves, respectively, and can act as specific antigens for identifying different nerve fascicles. Sections of the same type of nerve fascicles showed reproducibility with similar spectral features. Significant differences in the spectral properties, such as the intensity and breadth of the peak, were found between motor and sensory fascicles in the frequency regions of 1,088 cm(-1), 1,276 cm(-1), 1,439 cm(-1), 1,579 cm(-1), and 1,659 cm(-1). With the peak intensity ratio of 1.06 (I(1276)/I(1439)) as a standard, we could identify motor fascicles with a sensitivity of 88%, specificity of 94%, positive predictive value of 93%, and negative predictive value of 88%. In the range of 2,700 cm(-1) to 3,500 cm(-1), the half-peak width of the motor fascicles was narrow and sharp, whereas that of the sensory fascicles was relatively wider. A total of 91% of the peak features were in accordance with the identification standard. Motor and sensory fascicles exhibit different characteristics in Raman spectra, which are constant and reliable. Therefore, it is more effective than immunohistochemistry method in identifying different nerve fascicles according to the specific spectrum, and it possesses feasibility for clinical application.

Responses to magnetic stimuli recorded in peripheral nerves in the marine nudibranch mollusk Tritonia diomedea

Prior behavioral and neurophysiological studies provide evidence that the nudibranch mollusk Tritonia orients to the earth's magnetic field. Earlier studies of electrophysiological responses in certain neurons of the brain to changing ambient magnetic fields suggest that although certain identified brain cells fire impulses when the ambient field is changed, these neuron somata and their central dentritic and axonal processes are themselves not primary magnetic receptors. Here, using semi-intact animal preparations from which the brain was removed, we recorded from peripheral nerve trunks. Using techniques to count spikes in individual nerves and separately also to identify, then count individual axonal spikes in extracellular records, we found both excitatory and inhibitory axonal responses elicited by changes in the direction of ambient earth strength magnetic fields. We found responses in nerves from many locations throughout the body and in axons innervating the body wall and rhinophores. Our results indicate that primary receptors for geomagnetism in Tritonia are not focally concentrated in any particular organ, but appear to be widely dispersed in the peripheral body tissues.

Surgical Management of Recurrent Malignant Schwannoma of the Scalp

Localization of malignant schwannoma in the head and neck region is rare. Malignant schwannoma is a highly aggressive, slowly growing, encapsulated tumor of nerve sheath origin. The most common presentation of this tumor is a subcutaneous progressively enlarging mass with or without neurologic symptoms. These tumors arise from neurofibromas with or without von Recklinghausen disease, and most of the remains develop from peripheral nerve trunks. We report a case with recurrent malignant schwannoma of the scalp that is an uncommon presentation and discuss the clinicopathologic properties of this tumor.

Spatial Distribution of Nerve Fiber Pathology and Vasculitis in Microscopic Polyangiitis-Associated Neuropathy

We analyzed the 3-dimensional distribution of pathologic findings in 8 autopsied cases of neuropathy associated with microscopic polyangiitis. Necrotizing vasculitis was commonly and diffusely present in the epineurium of the sciatic/tibial and median nerves. Although findings of vasculitis were distributed diffusely in proximal to distal segments of the nerve trunks, marked loss of myelinated fibers occurred only from the middle to distal segments of these nerves. Neurons of the sensory and sympathetic ganglia were well preserved, as were myelinated fibers of the anterior and posterior spinal roots. Central fascicular nerve fiber degeneration, suggesting direct ischemic damage, occurred in restricted segments of the proximal-middle portion of the sciatic/tibial and median nerve trunks. Vasculitis was also seen in various visceral organs in all patients, but its distribution differed among individual patients; the severity of vasculitis in the other organs did not correlate with that in the peripheral nerves. The distinct spatial distribution pattern of nerve fiber degeneration, in contrast to the ubiquitous presence of vasculitis, suggested that the ischemic zone that directly damages nerve fibers is present in the proximal-middle portion of peripheral nerve trunks in microscopic polyangiitis.

Surgical repair of a 30 mm long human median nerve defect in the distal forearm by implantation of a chitosan-PGA nerve guidance conduit

This paper describes a clinical case study in which a chitosan/polyglycolic acid nerve guidance conduit (chitosan-PGA NGC) was utilized to repair a 30 mm long median nerve defect in the right distal forearm of a 55 year-old male patient. Thirty-six months after the nerve repair, the palm abduction of the thumb and the thumb-index digital opposition recovered, facilitating the patient to accomplish fine activities, such as handling chopsticks. Static two-point discrimination measured 14, 9 and 9 mm in the thumb, index and middle fingers of the right hand. Reproducible compound muscle action potentials were recorded on the right abductor pollicis. The ninhydrin test, a classical method for assessing sympathetic nerve function, showed partial recovery of the perspiration function of the injured thumb, index and middle fingers. This repair case suggested a possible strategy for the clinical reconstruction of extended defects in human peripheral nerve trunks by the implantation of chitosan-PGA NGCs.

Bilateral medial fingernail dystrophy as a presenting feature in a patient with leprosy

An 18 year old male student presented at the dermatology clinic complaining of discolouration, thickening, grooving and deformation of the medial three fingernails of both hands for the last 4 months. He was not involved in any manual work and denied that he bit his nails. There was no history of any major medical or surgical events in his recent past. Examination of the nails revealed opaque leukonychia of the distal nail plates of the fourth and fifth digits bilaterally. The affected nails also showed horizontally transverse grooves, blackish discolouration and roughness with a flattening of their normal contour. The right third fingernail was also affected similarly with a horizontal groove near the distal edge with discolouration of the nail plate. The left third fingernail showed less prominent changes, yet a partial horizontal groove was visible near the proximal end (Figure 1). A nail clipping immersed in 10% potassium hydroxide and fungal culture did not reveal any fungal elements. Blood sugar and X-ray of the hands were normal. This distribution of nail changes approximately matched the ulnar nerve distribution. Both ulnar nerves were found to be thickened on palpation while other peripheral nerve trunks were not enlarged. Bearing in mind the possibility of leprosy, diagnostic signs were

Avaliação de hansenianos tratados com esquema alternativo dose única ROM (rifampicina, ofloxacina e minociclina), após sete a nove anos

In 1997, after obtaining a combined multi-state double-blind randomly controlled clinical trial study from nine Indian centers involved in the treatment of Hansen's Disease, the Ministry of Health adapted the single dose ROM Therapy approach in those cases involving the treatment of a single skin lesion, paucibacillary leprosy without evidence of peripheral nerve trunk involvement and indication of negative baciloscope, in the Referral Centers in Brazil. The study aimed to evaluate the effectiveness of the single dose ROM Therapy approach in those patients who were treated from the period of 1997 to 1999 in the Ambulatory Dermatologic Unit in the Hospital in Vitória, ES. Fifty-four patients with tuberculoid and indeterminate leprosy were selected and treated with the single dose ROM Therapy approach. These patients were contacted from March 2006 up and until October 2006 for further clinical reevaluation. From the studies conducted, the following results were found to exist: 29 patients (85,2%; 95%CI: 70-100,4) were cured, 5 patients (14,7%; 95%CI: 7,4-22,0) relapsed, and 20 patients didn't return; however, there are no additional records of any notification of other treatment(s) in the State Department of Health's informational data banks. The study demonstrated a rate of cure of 90.8% and a rate of relapse of 9.2% after a period of seven to nine years using the single dose ROM Therapy approach. Additionally, this alternative treatment further demonstrated a better effectiveness for a single skin lesion smaller than four centimeters and with an appearance in less than five years.

Glio-neuronal and glio-glial syncytial cytoplasmic connections in peripheral nerve trunks of the crayfish Astacus leptodactylus

The paper considers various aspects of glial sheaths of neuritis in the crayfish peripheral nerve trunks and roots. There are revealed dotted glio-neurite tight junctions and a varicose deformation of the intercellular glio-neurite cleft. Rupture of membranes in the area of contact leads to formation of the glio-neurite pore (less than 10 nm) that is enlarged and forms wide (up to 240 nm) syncytial perforations. At the edge of perforation, either remnants of tight junctions are present or damaged membranes that fuse and are rounding. The lumen of perforations always contains residual membranous bodies in the form of vesicles. Their deviation from the median line can indicate a mutual translocation of substances of the glio- and neuroplasm. In the adjacent layers of the multilayer glial sheath there is noted a similar phenomenon of formation of the glio-glial syncytial connection terminating by fusion of neighbor glial layers, which is terminated by fusion of neighbor glial layers into the single lamina. The process begins from the varicose deformation of interglial clefts, which appears as a result of massive formation of dotted and expanded tight membranous contacts. As a result of transformation of ellipsoid varicose deformations into the spherical ones, syncytial pores (less than 10 nm) between them are formed, which are enlarged and break the paired gliolemmas into fragments. As a result, the adjacent glial layers are united. Since this process in intact animals occurs on the background of undamaged nerve structures, a suggestion is put forward about its reversibility and the functional nature.

The Microvascular Impact of Focal Nerve Trunk Injury

The microvascular supply of the peripheral nerve trunk may be rendered vulnerable by acute focal injuries, particularly if they are associated with direct injury to the epineurial blood supply. In this work we tracked the impact of three clinically relevant forms of focal nerve trunk injury on serial measures of epineurial weighted erythrocyte flux and endoneurial blood flow: short-length crush injuries, long-segmental crush injuries, and crush injuries with superimposed vascular stripping to model added direct epineurial damage. Red blood cell (RBC) flux was measured using quantitative multiple sampling laser doppler flowmetry, and endoneurial blood flow by microelectrode hydrogen clearance polarography. Both short and long crush injuries transiently reduced epineurial RBC flux, most prominently in long injuries, to 34% by 1 h after injury. The changes were less prominent when deeper flux was examined, whereas endoneurial blood flow was not altered by either injury. Long crush injury with added stripping of the epineurial blood supply was associated with more profound declines in epineurial RBC flux, to 16% by 3 h, with recovery at 14 days to 70% of that of the contralateral intact nerve trunk. There was, however, only a minimal impact on endoneurial flow: mild reductions immediately and at 1 h after injury, with rebound hyperemia by 48 h. Despite the presence of prominent epineurial ischemia, regenerative sprouting was not impaired by longer segmental injuries with or without epineurial vascular stripping. Axon sprouting was more prominent in both of these types of injuries compared to short-crush lesions. Taken together, these results indicate that focal nerve trunk injury is remarkably resistant to endoneurial ischemia, and that it can sustain regenerative sprouting in spite of prolonged alterations in the epineurial circulation. Approaches to augment epineurial microvascular viability after nerve injury may not support better regeneration.

Pain science and mobilisation of painful compressive neuropathies

Recent experimental investigation indicates that demyelination of peripheral nerve trunk and spinal nerve root neurones may be responsible for much of the abnormal pathology and, therefore, symptomatology of common peripheral entrapment or compressive neuropathies such as carpal tunnel syndrome. Studies suggest that repetitive relatively low level mechanical stimuli such as shear ('slide'/'glide') and stretch ('tension') mimic the clinical situation, and act directly on Schwann cells. This causes Schwann cells to dedifferentiate (lose special form, function), proliferate (divide) and undergo apoptosis (programmed cell death). As part of the process of stimulus-induced demyelination Schwann cells down-regulate myelin-forming proteins (and up-regulate nonmyelin markers). Downregulation of myelin protein together with upregulation of a growth cone molecule (GAP-43), appear to be involved in the sprouting of unmyelinated afferents seen with compressive neuropathy. In addition, the expression by Schwann cells of a factor that is 'trophic' for unmyelinated afferents, probably contributes to a general increase in the ratio of nociceptors to proprioceptors. Presumably such Schwann cell-mediated change in afferent phenotype facilitates the production of pain. Importantly, at the time these and other pathological events are occurring the usual triggers for cell dedifferentiation, proliferation and apoptosis – namely, axon damage, Wallerian degeneration and macrophage signalling – are absent. Together the evidence supports the proposal that compressive peripheral neuropathy is a mechanically initiated (maintained?) Schwann cell-mediated condition. As such, this proposal is relevant to movement-based therapies that use 'diagnostic' and therapeutic mechanical stimuli in the management of peripheral compressive neuropathies.

Generalized Mechanical Pain Sensitivity Over Nerve Tissues in Patients With Strictly Unilateral Migraine

No study has previously analyzed pressure pain sensitivity of nerve trunks in migraine. This study aimed to examine the differences in mechanical pain sensitivity over specific nerves between patients with unilateral migraine and healthy controls. Blinded investigators assessed pressure pain thresholds (PPT) over the supra-orbital nerves (V1) and peripheral nerve trunks of both upper extremities (median, radial, and ulnar nerves) in 20 patients with strictly unilateral migraine and 20 healthy matched controls. Pain intensity after palpation over both supra-orbital nerves was also assessed. A pressure algometer was used to quantify PPT, whereas a 10-point numerical pain rate scale was used to evaluate pain to palpation over the supra-orbital nerve. The analysis of covariance revealed that pain to palpation over the supra-orbital nerve was significantly higher (P<0.001) on the symptomatic side (mean: 3.4, SD: 1.5) as compared with the nonsymptomatic side (mean: 0.5, SD: 1.2) in patients with migraine and both the dominant (mean: 0.2, SD: 0.4) and nondominant (mean: 0.3, SD: 0.5) sides in healthy controls. PPT assessed over the supra-orbital nerve on the symptomatic side (mean: 1.05, SD: 0.2 kg/cm) was significantly lower (P<0.05) than PPT measurements on the nonsymptomatic side (mean: 1.35, SD: 0.3 kg/cm) and either the dominant (mean: 1.9, SD: 0.2 kg/cm) or nondominant (mean: 1.9, SD: 0.3 kg/cm) sides in controls (P<0.001). Finally, PPT assessed over the median, ulnar, and radial nerves were significantly lower in patients with migraine as compared with controls (P<0.001), without side-to-side differences (P>0.6). In patients with unilateral migraine, we found increased mechano-sensitivity of the supra-orbital nerve on the symptomatic side of the head. Outside the head, the same patients showed increased mechano-sensitivity of the main peripheral nerves of both upper limbs, without asymmetries. Such diffuse hypersensitivity of the peripheral nerves lends further evidence to the presence of a state of hyperexcitability of the central nervous system in patients with unilateral migraine.