Peripheral nerve regeneration through nerve conduits evokes differential expression of growth-associated protein-43 in the spinal cord

Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.

Unilateral peripheral neuropathic pain: The role of neurodiagnostic skin biopsy

According to the current definition of neuropathic pain("pain arising as a direct consequence of a lesion or disease affecting the somatosensory system"), the demonstration of a lesion or disease involving the somatosensory system is mandatory for the diagnosis of definite neuropathic pain. Although several methods are currently available for this aim, none is suitable for every type of disease(or lesion). Neurodiagnostic skin biopsy(NSB) is a relatively new technique for the diagnosis of peripheral nerve lesions. It is an objective method, completely independent from the patient's complaining, based on immunohistochemical staining techniques that allow measurement of the density of the epidermal nerve fibers, currently considered the free nerve endings of small diameter(A-delta and C) afferent fibers. NSB has the important property of being used to investigate the skin, allowing obtaining a diagnosis of small fiber axonal neuropathy of peripheral nerves supplying every body part covered by skin. This feature appears to be very important, particularly in cases of unilateral nerve lesions, because it allows going beyond the possibilities of neurophysiological tests which are available only for a limited number of peripheral nerves. All these characteristics make NSB a precious instrument for the diagnosis of peripheral unilateral neuropathic pain.

Dynamic mechanical allodynia following finger amputation:Unexpected skin hyperinnervation

The development of chronic pain after amputations is not an uncommon event. In some cases the most disabling problem is represented by the symptom called dynamic mechanical allodynia, characterized by the painful sensation evoked by gently stroking the skin. Despite the growing interest in understanding pain mechanisms, little is known about the mechanism sustaining this peculiar type of pain. We present here the case of a 53-year-old female patient who complained of severe tactile allodynia in the hand after amputation of her left second finger, resistant to several medical and surgical treatments. In order to gain information about the pain mechanism, two neurodiagnostic skin biopsies were obtained from the area of tactile allodynia and from the contralateral, normal skin area. Skin biopsies showed an unexpected increased innervation of the allodynic skin compared to the contralateral, normal skin area(+ 80.1%). Hyperinnervation has been proposed as a mechanism of pain following nerve lesions, but the increased innervation described here could be also attributed to neuronal plasticity occurring in chronic inflammatory conditions. Independently from the uncertain cause of the epidermal hyperinnervation, in this patient we tried to reduce the elevated number of epidermal nerve fibres by treating the skin with topical capsaicin(0.075%) three times a day, and obtained a persistent pain relief. In conclusion, neurodiagnostic skin biopsy might represent an useful tool for detecting derangements of epidermal innervation in patients with dynamic mechanical allodynia and can help to select an individually tailored therapeutic strategy in such difficult clinical conditions. Further studies are needed to clarify this issue and try to gain better understanding of chronic pain mechanisms in patients who underwent finger amputation.

Where is hidden the ghost in phantom sensations?

The term phantom sensations(PS) refers to sensations in a missing body part. They are almost universal in amputees and can be both painful and not painful. Although PS have been frequently described in limb amputees, they can also occur in other clinical conditions and several pathophysiological interpretations have been proposed, with a predominance of theories based on a central origin. Actually, different mechanisms are able to create a phantom sensation. After an amputation, PS are frequently generated by the genesis of ectopic action potentials in the interrupted nerve fibers but the PS generator can also be more proximal. Sometimes PS are not created by the stimulation of somatosensory fibers with a missing territory, but they can be the result of central sensitization or neuroplastic changes that allow for the convergence of impulses coming from different body parts(referred sensations), one of which is missing. In conclusion, PS can be generated by both neuropathic and non-neuropathic mechanisms developed in the amputated body part or in other parts of the nervous system. Since these mechanisms are not pathognomonic of amputation there are no hidden ghosts to look for in phantom sensations. The only interpretative rule is just to follow the pathophysiological principles.

肉毒素治疗掌部多汗症后无代偿性出汗

Background: Primary focal hyperhidrosis is caused by excessive secretion by eccrine sweat glands, usually at the palms, soles and axillae. The underlying mechanism is unclear. In recent years botulinum toxin A has emerged as a useful treatment. Compensatory sweating, which is a major problem in many patients who have undergone transthoracic endoscopic sympathectomy for hyperhidrosis, has only rarely been reported after botulinum toxin. However, this potential side-effect of botulinum toxin treatment has not been systematically examined. Objectives: To investigate if treatment with botulinum toxin A in hyperhidrotic hands may cause compensatory sweating at other skin locations. Methods: In 17 patients with a history of palmar hyperhidrosis repeated measurements of evaporation were made before and up to 6 months after treatment of the hands with botulinum toxin A. Recordings were made at 16 skin areas and compared with subjective estimates of sweating. Results: Following treatment, palmar evaporation decreased markedly and then returned slowly towards pretreatment values, but was still significantly reduced 6 months after treatment. No significant increase of sweating was found after treatment in any nontreated skin area. Conclusions: Successful treatment of palmar hyperhidrosis with botulinum toxin does not evoke compensatory hyperhidrosis in nontreated skin territories.