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Pain has variously been used as a means of punishment, extracting information, or testing commitment, as a tool for education and social control, as a commodity for sacrifice, and as a draw for sport and entertainment. Attitudes concerning these uses have undergone major changes in the modern era. Normative convictions on what is right and wrong are generally attributed to religious tradition or to secular-humanist reasoning. Here, we elaborate the perspective that ethical choices concerning pain have much earlier roots that are based on instincts and brain-seated empathetic responses. They are fundamentally a function of brain circuitry shaped by processes of Darwinian evolution. Social convention and other environmental influences, with their idiosyncrasies, are a more recent, ever-changing overlay. We close with an example in which details on the neurobiology of pain processing, specifically the question of where in the brain the experience of pain is generated, affect decision making in end-of-life situations. By separating innate biological substrates from culturally imposed attitudes (memes), we may arrive at a more reasoned approach to a morality of pain prevention.

OBJECTIVE Guglielmi detachable coil treatment is becoming an accepted alternative to microsurgical clipping for select intracerebral aneurysms. Resolution of oculomotor nerve paresis (ONP) after endovascular packing was claimed to be complete in two prior series, with three and six cases. We describe the evolution of ONP after Guglielmi detachable coil treatment of posterior communicating artery aneurysms, and we search for endovascular and patient factors correlated with the degree of functional nerve recovery. METHODS Twelve cases of ONP attributable to posterior communicating artery aneurysms were treated with Guglielmi detachable coils between 1999 and 2002. Eleven patients were available for follow-up monitoring. The degree of ONP was recorded at admission, at discharge, after 3 months, and at yearly intervals thereafter. The size of the aneurysm, the duration of ONP before coiling, the degree of coiling, age, and the presence of other microvascular risk factors were correlated with the degree of nerve recovery. RESULTS Complete resolution of ONP did not occur in any of the 11 cases in this series. However, residual oculomotor nerve deficits did not cause diplopia with primary gaze for 10 of 11 patients. Clinically significant ptosis did not persist for any of the patients. The pupil remained minimally affected in all cases. CONCLUSION Although mass effect remains after endovascular packing, oculomotor nerve dysfunction improves comparably to the recovery observed after surgical clipping. Contrary to previous reports, typical residual oculomotor nerve deficits persist. Older age and the presence of microvascular risk factors seem to be detrimental to ONP recovery.

Object. Recent progress in the understanding of abnormal electrical behavior in injured sensory neurons motivated an examination, at the ultrastructural level, of trigeminal roots of patients with trigeminal neuralgia (TN). Methods. In 12 patients biopsy specimens of trigeminal root were obtained during surgery for microvascular decompression. Pathological changes in tissue included axonopathy and axonal loss, demyelination, a range of less severe myelin abnormalities (dysmyelination), residual myelin debris, and the presence of excess collagen, including condensed collagen masses in two cases. Within zones of demyelination, groups of axons were often closely apposed without an intervening glial process. Pathological characteristics of nerve fibers were clearly graded with the degrees of root compression noted at operation. Pain also occurred, however, in some patients who did not appear to have a severe compressive injury. Conclusions. Findings were consistent with the ignition hypothesis of TN. This model can be used to explain the major positive and negative symptoms of TN by axonopathy-induced changes in the electrical excitability of afferent axons in the trigeminal root and of neuronal somata in the trigeminal ganglion. The key pathophysiological changes include ectopic impulse discharge, spontaneous and triggered afterdischarge, and crossexcitation among neighboring afferents.

There are no satisfactory animal models of trigeminal neuralgia, and it is difficult to obtain essential data from patients. However, trigeminal neuralgia presents with such idiosyncratic signs and symptoms, and responds to so distinctive a set of therapeutic modalities, that scientific deduction can be used to generate likely hypotheses. The ignition hypothesis of trigeminal neuralgia is based on recent advances in the understanding of abnormal electrical behavior in injured sensory neurons, and new histopathologic observations of biopsy specimens from patients with trigeminal neuralgia who are undergoing microvascular decompression surgery. According to the hypothesis, trigeminal neuralgia results from specific abnormalities of trigeminal afferent neurons in the trigeminal root or ganglion. Injury renders axons and axotomized somata hyperexcitable. The hyperexcitable afferents, in turn, give rise to pain paroxysms as a result of synchronized afterdischarge activity. The ignition hypothesis accounts for the major positive and negative signs and symptoms of trigeminal neuralgia, for its pathogenesis, and for the efficacy of treatment modalities. Proof, however, awaits the availability of key experimental data that can only be obtained from patients with trigeminal neuralgia.

Idiosyncrasies of trigeminal neuralgia provide both clues and constraints on candidate hypotheses concerning the underlying neural mechanism. After reviewing the key clinical aspects of the disease, we propose here a novel hypothesis based on recent findings from experimental nerve-injury preparations. The hypothesis states that trigger stimuli set off bursts of activity in a small cluster of trigeminal ganglion (TRG) neurons that have been rendered hyperexcitable as a result of TRG or trigeminal root damage. Activity then spreads from this "TRG ignition focus" to encompass more widespread portions of the ganglion. After a brief period of autonomous firing (seconds to minutes), activity is quenched and a refractory period is initiated by an intrinsic suppressive (hyperpolarizing) process engaged as a result of the rapid firing. The primary abnormality resides in the TRG and trigeminal root, rather than in the skin or the CNS. Because of this, sensation is essentially normal between periods of ectopic paroxysmal TRG discharge.

Transseptal transsphenoidal surgery of pituitary tumors is a well-established surgical technique. The sublabial approach and the open rhinoplasty approach are most commonly used. In both cases, the surgical avenue is along the entire length of the nasal septum, removing both nasal cartilage and the vomer. Septal perforations and upper dental anesthesia are frequent complications of the standard approaches. We describe our initial experience in using the nasal endoscope for the first stage of the operation.A nasal endoscope was used to open the anterior wall of the sphenoid sinus. Our initial incision was in the posterior third of the septum, removing only the vomer. After the sphenoid sinus was opened, we inserted a speculum and proceeded with the operation with an operating microscope. After the speculum was in place, it was easier to proceed with the microscope, which allows binocular vision and bimanual operation.The procedure was used for our most recent 14 consecutive patients with pituitary adenomas. No complications related to the approach were encountered for any of the patients in follow-up monitoring.The endoscopic transseptal approach to the sphenoid sinus for pituitary surgery was found to be easy, time-saving, and without septal or sublabial complications.

When faced with mortality people tend to turn to their religious heritage, even if they are secularized. Ethical issues are deeply influenced by the religious background of our societies. In this essay we wish to examine the concept of death from a Jewish religious perspective. With the emergence of brain death criteria driven by the advances in medical technology, Jewish religious interpretation adjusted to take into account the possibilities of modern medical technology. While traditionalist elements cling to older interpretations, a process of ethical evolution, similar to that in other societies, has led to the widespread acceptance of brain death criteria for the purpose of organ donation in Israel.

✓ A number of noninvasive methods used to measure intracranial pressure (ICP) have been proposed in the literature. For a variety of reasons, however, none of these have displayed significant practical applicability. The authors describe their development of a new, computerized, portable device based on tissue resonance analysis (TRA) technology for the noninvasive monitoring and measurement of ICP. In response to the heart beat, the soft tissue and fluid compartments of the brain each exhibit characteristic vibration and mechanical resonant responses that radiate through the organs and tissues of the body. Patterns of vibration and mechanical resonance of various body organs and tissues are different and provide the possibility of extracting new and specific information in a noninvasive fashion. According to the TRA approach, ICP is dependent on the value of the dominant secondary (mechanical) resonance level of brain tissue. By digitally processing a reflected ultrasound signal (by using a concave ultrasonography probe with a carrier frequency of 1 MHz) from the third ventricle, the authors obtained a digital high-resolution echopulsogram, which visually is equivalent to ICP waves that are obtained invasively. The fast Fourier relationship of electrocardiogram and echopulsogram waves allowed the derivation of the secondary mechanical resonance levels. The authors developed a formula for a quantitative, noninvasive measurement of ICP, which uses information regarding multiple components of the intracranial space—both mechanical (secondary resonance) and physiological (time required for transfer of arterial blood to venous blood through brain tissue)—and the relationship between these components. A comparison of invasive and noninvasive ICP measurements was made during blinded trials in 40 patients with various diseases of the central nervous system, and ranges of ICP were measured from 1 to 66 mm Hg. The ICP values obtained using the two methods were highly correlated (r = 0.99), without a statistically significant difference between simultaneously obtained readings (p = 1). By using an integrative approach that reflects all components of the intracranial compartment, TRA allows for accurate noninvasive recordings of ICP. This method has significant advantages over other noninvasive technologies reported to date.

✓ Optical and electron microscopic examinations were made of a biopsy sample of the ninth and 10th cranial nerves obtained during posterior fossa surgery for the relief of pain in a patient suffering from glossopharyngeal neuralgia (GN). Pathological findings, which were restricted to a small fraction of fascicles in the nerves, included large patches of demyelinated axons in close membrane-to-membrane apposition to one another and zones of less severe myelin damage (dysmyelination). These observations, in the light of similar morphological changes observed in biopsy samples excised from patients with trigeminal neuralgia, and new information on the pathophysiological characteristics of injured peripheral nerve axons, can account for much of the symptomatology of GN.

Nerve injury sometimes triggers neuropathic pain states that are exacerbated by sympathetic efferent activity. A classic example is causalgia. The mechanism of coupling between sympathetic efferent activity and the afferent discharge responsible for pain sensation is a subject of controversy. Some authors hold to the 'direct coupling hypothesis' which proposes that noradrenaline (NA), released from sympathetic varicosities, acts directly on alpha-adrenoreceptors located in the membrane of injured primary afferents. Others believe that coupling is indirect; that the effects of NA are mediated by additional, non-adrenergic, chemical substances and their receptors (the 'indirect coupling hypothesis'). For example, it has been proposed that in inflamed skin NA acts back on the sympathetic endings which, secondarily, release a prostanoid mediator which sensitizes afferent endings. We report that the responsiveness of injured afferent axons to systemically applied NA persists, and in fact increases in prevalence, in rats that underwent prior chemical or surgical sympathectomy. The observation of adrenosensitivity in injured afferents in the absence of sympathetic postganglionic endings is consistent with the direct coupling hypothesis, which associates adrenosensitivity with the injured afferent axon. It is not consistent with the indirect coupling hypothesis which requires the presence of sympathetic endings as a source for NA-evoked prostanoid release.

Publisher Summary This chapter describes pathophysiologic processes through which damaged nerves can come to contribute actively to chronic pain both by injecting abnormal discharge into the nervous system, and by amplifying and distorting naturally generated signals. Pathophysiologic changes in the peripheral nervous system (PNS) may cause neuropathic and radiculopathic pain. Thereafter irritation or damage to peripheral nerves or sensory roots triggers the development of distinctive clinical syndromes which include both negative and positive symptoms. The data presented in the chapter suggests that the primary pathophysiologic change in injured nerves, spinal roots, and dorsal root ganglias is an increase in electrical excitability. The probable cause is abnormal differentiation of the axonal membrane at the cut nerve end, at sites of demyelination, and in axotomized sensory neurons. Damaged nerves are capable of generating rhythmic discharge at ectopic pacemaker sites, providing a signal for detection. Also associated with abnormal impulse generation in damaged nerves are several processes that can amplify normal or pathophysiologic impulse discharge. There is a fundamental difference between the mechanisms of normal and neuropathic pain. Normal pain arises from acute or chronic stimulation of normal afferent nociceptor endings by intense stimuli, while neuropathic pain occurs spontaneously, or in response to weak stimuli because of abnormalities of neural excitability.

Autotomy in nerve injured rats has been put forward as an animal model in a broad range of chronic neuralgic pain. We have examined the effect of glycerol, a new and promising therapeutic agent for trigeminal neuralgia, on this animal model. A single dose of glycerol, alcohol or saline was injected directly into experimental sciatic nerve neuromas in rats via a chronically implanted cannula. Injections were made either at the time of nerve injury or 2 weeks afterwards. Both forms of glycerol treatment caused a significant reduction in autotomy behavior relative to saline. Alcohol also suppressed autotomy, but it was less effective than glycerol.

Autotomy has been suggested as an animal model of chronic pain. It starts about a week or two postoperatively and develops until 10 weeks after nerve section. This behaviour is thought to be triggered by activity of sensory fibres ending in a neuroma. Here we suggest to utilize it in combination with a novel drug delivery system which enables a direct and exclusive access of the drug to the neuroma. Alteration in the autotomy behaviour can then be related to the exclusive topical action on the sensory fibres within the neuroma. The sciatic nerve is transsected and its proximal end inserted into a PE tube sealed distally. A second, smaller tube originates in a wound exit in the back of the animal and subcutaneously leads into the large tube, where it is fixed by glue to the inner wall. Thus, the end of the smaller tube is juxtaposed to the nerve end. During the following weeks a neuroma develops within the tube. The resulting autotomy scores are then examined weekly. At various times after the operation, under light anaesthesia, drugs can be injected into the tube and the effect on the autotomy behaviour is monitored. An example is given, describing the autotomy suppressive effects of glycerol and alcohol, injected to different groups of rats immediately after the operation and compared to an injection 14 days postoperatively. This method is suggested as a pharmaco-behavioural assay for the assessment of the analgetic efficacy of drugs for chronic pain.

✓ A case is reported in which systemic Weber-Christian disease presented as a dural mass causing the signs and symptoms of increased intracranial pressure. The literature and possible pathogenesis of this entity are discussed.