Inducing Ulnar Nerve Function while Eliminating Claw Hand and Reducing Chronic Neuropathic Pain.

Ulnar nerve injury induces chronic neuropathic pain and is frequently devastating due to loss of cupping the hand around objects (finger clawing) and diminished grip strength. There is little chance of restoring good function, eliminating finger clawing, or reducing the pain. A novel technique was tested for its efficacy in promoting ulnar nerve function and reducing finger clawing and chronic neuropathic pain. A 25-year-old subject presented 5.7 months after a wrist gunshot that created three nerve gaps proximal to the deep ulnar nerve branch. He sought restoration of function due to developing ulnar nerve injury-induced claw hand and increasingly severe chronic neuropathic pain. After resection of the scarred nerve tissue, each gap was 10 cm long. The gaps were bridged with two nonreversed sural nerve grafts within a PRP-filled NeuroMend collagen tube (Collagen Matrix, Oakland, N.J.). Some axons regenerated entirely across all three 10-cm-long repaired nerve gaps, restoring excellent topographically correct sensitivity of S4, including two-point discrimination of 4 mm, good M4 motor function, and full ROM. The ulnar nerve injury-induced finger clawing was eliminated, and the chronic neuropathic pain of 7 was reduced to 0 on a 0-10 validated scale and did not return over the following 3.75 years. Thus, this novel technique induces good sensory and motor function, despite repairing three 10-cm-long nerve gaps while eliminating ulnar nerve injury-induced hand clawing and chronic neuropathic pain. Further studies are required to determine whether the effects were due to PRP.

Coping with Phantom Limb Pain.

Phantom limb pain is a chronic neuropathic pain that develops in 45-85% of patients who undergo major amputations of the upper and lower extremities and appears predominantly during two time frames following an amputation: the first month and later about 1 year. Although in most patients the frequency and intensity of pain diminish over time, severe pain persists in about 5-10%. It has been proposed that factors in both the peripheral and central nervous systems play major roles in triggering the development and maintenance of pain associated with extremity amputations. Chronic pain is physically and mentally debilitating, affecting an individual's capacity for self-care, but also diminishing an individual's daily capacity for personal and economic independence. In addition, the pain may lead to depression and feelings of hopelessness. A National Center for Biotechnology Information study found that in the USA alone, the annual cost of dealing with neuropathic pain is more than $600 billion, with an estimated 20 million people in the USA suffering from this condition. Although the pain can be reduced by antiepileptic drugs and analgesics, they are frequently ineffective or their side effects preclude their use. The optimal approach for eliminating neuropathic pain and improving individuals' quality of life is the development of novel techniques that permanently prevent the development and maintenance of neuropathic pain, or that eliminate the pain once it has developed. What is still required is understanding when and where an effective novel technique must be applied, such as onto the nerve stump of the transected peripheral axons, dorsal root ganglion neurons, spinal cord, or cortex to induce the desired influences. This review, the second of two in this journal volume, examines the techniques that may be capable of reducing or eliminating chronic neuropathic pain once it has developed. Such an understanding will improve amputees' quality of life by blocking the mechanisms that trigger and/or maintain PLP and chronic neuropathic pain.

Origins of Phantom Limb Pain.

Phantom limb pain (PLP) is a chronic neuropathic pain occurring in 45-85% of patients who undergo major amputations of the upper and lower extremities. Chronic pain is physically and mentally debilitating, affecting an individual's potential for self-care and the performance of daily living activities essential for personal and economic independence. In addition, chronic pain may lead to depression and feelings of hopelessness. A National Center for Biotechnology Information study found that in the USA alone, the annual cost of dealing with neuropathic pain is more than $600 billion, with an estimated 20 million people in the USA suffering this condition. PLP manifest predominantly during two time frames post-amputation: during days to a month and again at around 1 year. In most patients, the frequency and intensity of the chronic neuropathic pain diminish over time, but severe pain persists in about 5-10% of patients. The development and maintenance of neuropathic pain is attributed to extremity amputations causing changes in peripheral axon properties and neuronal circuitry in both the peripheral and central nervous systems: peripheral axons, dorsal root ganglia, the spinal cord, and the cortex. However, it is not clear how the changes in neuronal properties in these different locations affect neuropathic pain. Is pain initiated by one set of post-amputation changes while the pain is maintained by another set of changes? If one set of amputation-induced changes, such as those of peripheral axons, are reverted to normal, is the chronic pain reduced or eliminated, while reversing another set of neuronal changes and neuronal circuits to normal do not reduce or eliminate the pain? Or, must all the amputation-induced changes be reverted to normal for pain to be eliminated? While this review examines the mechanisms underlying the induction or maintenance of PLP, it is beyond its scope to examine the mechanisms that may permanently reduce or eliminate neuropathic pain. This paper is the first of two reviews in this journal and deals with the causes of chronic PLP development and maintenance, while the second review examines potential mechanisms that may be responsible for promoting the capacity to coping with PLP by reducing or eliminating it.

Photobiomodulation in promoting wound healing: a review.

Despite diverse methods being applied to induce wound healing, many wounds remain recalcitrant to all treatments. Photobiomodulation involves inducing wound healing by illuminating wounds with light emitting diodes or lasers. While used on different animal models, in vitro, and clinically, wound healing is induced by many different wavelengths and powers with no optimal set of parameters yet being identified. While data suggest that simultaneous multiple wavelength illumination is more efficacious than single wavelengths, the optimal single and multiple wavelengths must be better defined to induce more reliable and extensive healing of different wound types. This review focuses on studies in which specific wavelengths induce wound healing and on their mechanisms of action.

Platelet-Rich Plasma Promotes Axon Regeneration, Wound Healing, and Pain Reduction: Fact or Fiction.

Platelet-rich plasma (PRP) has been tested in vitro, in animal models, and clinically for its efficacy in enhancing the rate of wound healing, reducing pain associated with injuries, and promoting axon regeneration. Although extensive data indicate that PRP-released factors induce these effects, the claims are often weakened because many studies were not rigorous or controlled, the data were limited, and other studies yielded contrary results. Critical to assessing whether PRP is effective are the large number of variables in these studies, including the method of PRP preparation, which influences the composition of PRP; type of application; type of wounds; target tissues; and diverse animal models and clinical studies. All these variables raise the question of whether one can anticipate consistent influences and raise the possibility that most of the results are correct under the circumstances where PRP was tested. This review examines evidence on the potential influences of PRP and whether PRP-released factors could induce the reported influences and concludes that the preponderance of evidence suggests that PRP has the capacity to induce all the claimed influences, although this position cannot be definitively argued. Well-defined and rigorously controlled studies of the potential influences of PRP are required in which PRP is isolated and applied using consistent techniques, protocols, and models. Finally, it is concluded that, because of the purported benefits of PRP administration and the lack of adverse events, further animal and clinical studies should be performed to explore the potential influences of PRP.

Improving the ability to eliminate wounds and pressure ulcers.

Pressure ulcers can be initiated by as little as 2 hours of constant pressure on the ski, that blocks blood circulation causing the skin and underlying tissues to die, leading to an open wound that never heals, but continues to grow in diameter and depth, and frequently jeopardizes patients' lives. Despite the application of many diverse techniques, pressure ulcers remain exceptionally difficult to heal because many ulcer elimination techniques have minimal effects, and although other techniques may appear to be effective, the evidence supporting their efficacy is weak. However, increasing evidence indicates that other techniques, such as the application of platelet-rich plasma, vacuum assisted closure, electrical stimulation, and hyperbaric oxygen therapy are effective and should be substituted for the older techniques. This review describes different standard and novel techniques that have been tested for eliminating pressure ulcers and discusses the relative efficacy of these techniques.

Platelet-rich plasma and the elimination of neuropathic pain.

Peripheral neuropathic pain typically results from trauma-induced nociceptive neuron hyperexcitability and their spontaneous ectopic activity. This pain persists until the trauma-induced cascade of events runs its full course, which results in complete tissue repair, including the nociceptive neurons recovering their normal biophysical properties, ceasing to be hyperexcitable, and stopping having spontaneous electrical activity. However, if a wound undergoes no, insufficient, or too much inflammation, or if a wound becomes stuck in an inflammatory state, chronic neuropathic pain persists. Although various drugs and techniques provide temporary relief from chronic neuropathic pain, many have serious side effects, are not effective, none promotes the completion of the wound healing process, and none provides permanent pain relief. This paper examines the hypothesis that chronic neuropathic pain can be permanently eliminated by applying platelet-rich plasma to the site at which the pain originates, thereby triggering the complete cascade of events involved in normal wound repair. Many published papers claim that the clinical application of platelet-rich plasma to painful sites, such as muscle injuries and joints, or to the ends of nerves evoking chronic neuropathic pain, a process often referred to as prolotherapy, eliminates pain initiated at such sites. However, there is no published explanation of a possible mechanism/s by which platelet-rich plasma may accomplish this effect. This paper discusses the normal physiological cascade of trauma-induced events that lead to chronic neuropathic pain and its eventual elimination, techniques being studied to reduce or eliminate neuropathic pain, and how the application of platelet-rich plasma may lead to the permanent elimination of neuropathic pain. It concludes that platelet-rich plasma eliminates neuropathic pain primarily by platelet- and stem cell-released factors initiating the complex cascade of wound healing events, starting with the induction of enhanced inflammation and its complete resolution, followed by all the subsequent steps of tissue remodeling, wound repair and axon regeneration that result in the elimination of neuropathic pain, and also by some of these same factors acting directly on neurons to promote axon regeneration thereby eliminating neuropathic pain.

Hyperbaric oxygen therapy: can it prevent irradiation-induced necrosis?

Radiosurgery is an important non-invasive procedure for the treatment of tumors and vascular malformations. However, in addition to killing target tissues, cranial irradiation induces damage to adjacent healthy tissues leading to neurological deterioration in both pediatric and adult patients, which is poorly understood and insufficiently treatable. To minimize irradiation damage to healthy tissue, not the optimal therapeutic irradiation dose required to eliminate the target lesion is used but lower doses. Although the success rate of irradiation surgery is about 95%, 5% of patients suffer problems, most commonly neurological, that are thought to be a direct consequence of irradiation-induced inflammation. Although no direct correlation has been demonstrated, the appearance and disappearance of inflammation that develops following irradiation commonly parallel the appearance and disappearance of neurological side effects that are associated with the neurological function of the irradiated brain regions. These observations have led to the hypothesis that brain inflammation is causally related to the observed neurological side effects. Studies indicate that hyperbaric oxygen therapy (HBOT) applied after the appearance of irradiation-induced neurological side effects reduces the incidence and severity of those side effects. This may result from HBOT reducing inflammation, promoting angiogenesis, and influencing other cellular functions thereby suppressing events that cause the neurological side effects. However, it would be significantly better for the patient if rather than waiting for neurological side effects to become manifest they could be avoided. This review examines irradiation-induced neurological side effects, methods that minimize or resolve those side effects, and concludes with a discussion of whether HBOT applied following irradiation, but before manifestation of neurological side effects may prevent or reduce the appearance of irradiation-induced neurological side effects.

Hyperbaric oxygen therapy and promoting neurological recovery following nerve trauma.

There is a constant search for new techniques that induce more extensive and rapid wound healing. Hyperbaric oxygen therapy (HBO2T) involves placing a patient in a sealed chamber and elevating its pressure several-fold above ambient air pressure while the patient breathes 100% oxygen. HBO2T induces a number of physiological actions, and which wounds are selected for HBO2T depends on the specific actions of HBO2T relative to the wound's healing requirements. Although nerve traumas are not yet indicated for HBO2T, there are many animal and clinical examples showing the benefits of HBO2T in inducing neurological recovery following nerve trauma. This review examines the general mechanisms required to induce wound healing and the actions of HBO2T which meet these requirements. It then examines the requirements for inducing axon regeneration and how many are met by HBO2T. Finally, we discuss anecdotal evidence that HBO2T enhances the rate and extent of axon regeneration in both animal models and clinically. Weconclude that HBO2T triggers most of the mechanisms required to induce axon regeneration.

Hyperbaric oxygen treatment to eliminate a large venous air embolism: a case study.

Gas embolism, the entry of gas into vascular structures, can result in serious morbidity and death. It is an inadvertent clinical problem, but it also occurs in non-clinical environments. Gas embolisms result from procedures performed in almost all clinical specialties, thus making it a problem about which all clinicians should be aware. In most cases, gas embolism is air embolism, although it can result from the introduction of gases such as carbon dioxide, nitrous oxide and nitrogen. Gas embolism takes two forms, venous and arterial, distinguished by the mechanism of gas entry and the site where the emboli ultimately lodge. Techniques used to eliminate embolisms including administration of 100% oxygen, placing the patient in lateral decubitus, and Trendelenburg position for no longer than 10 minutes, removing the embolism with a catheter, surfactants and hyperbaric oxygen therapy (HBO2T). For venous gas embolisms surgical removal is recommended, while for arterial embolisms, HBO2T is highly recommended. Here we report on a patient who inadvertently received a venous infusion of 150 ml air resulting in a major embolism, and who underwent HBO2T, recovered well, and suffered no adverse events. This result suggests that it is important to consider HBO2T as a recommended application for patients with venous embolisms.

The role of hyperbaric oxygen therapy in enhancing the rate of wound healing with a focus on axon regeneration.

Wounds have always afflicted humanity causing pain, suffering and death, and for thousands of years humans have tested and developed various techniques for their ability to induce wound healing. Hyperbaric oxygen therapy (HBOT) refers to placing a patient or their extremity in a chamber in which the pressure is raised several fold above ambient air pressure and the ambient air is substituted with 100% oxygen. HBOT is effective in enhancing the rate and effectiveness of healing of a variety of wounds and injuries. The mechanisms by which HBOT acts are well understood. An important question about HBOT is whether it can heal another is type of wound, nerves after trauma? This review primarily discusses mechanisms by which HBOT induces the complex process of wound healing. It then examines how some of these mechanisms are also involved in promoting axon regeneration. Finally it presents anecdotal evidence suggesting that HBOT promotes axon regeneration, but notes that more extensive and thorough studies are required to determine whether HBOT induces axon regeneration.