MUTZ-3, a monocytic model cell line for interleukin-4 and lipopolysaccharide studies

The afferent pathways of discogenic low-back pain have not been fully investigated. We hypothesised that this pain was transmitted mainly by sympathetic afferent fibres in the L2 nerve root, and in 33 patients we used selective local anaesthesia of this nerve. Low-back pain disappeared or significantly decreased in all patients after the injection. Needle insertion provoked pain which radiated to the low back in 23 patients and the area of skin hypoalgesia produced included the area of pre-existing pain in all but one. None of the nine patients with related sciatica had relief of that component of their symptoms. Our findings show that the main afferent pathways of pain from the lower intervertebral discs are through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Discogenic low-back pain should be regarded as a visceral pain in respect of its neural pathways. Infiltration of the L2 nerve is a useful diagnostic test and also has some therapeutic value.     

Cutaneous nociceptive facilitation of Ib heteronymous pathways to lower limb motoneurones in humans

The effects of tonic pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis (GM) to the soleus (Sol) and to the quadriceps (Q) muscles were investigated in four healthy human subjects. Tonic pain stimulation was performed by subcutaneous injection of 0.5 mg levo-ascorbic acid or vitamin C (L-LAS) in a volume of 0.5 ml on the dorsal surface of the ipsilateral foot. The mean curve of L-AS-induced pain sensation showed a steep rising phase reaching maximum intensity at 2-3 min, followed by a slow decay phase lasting about 15-20 min. Between about 5 and 20 min after injection, there was evidence of pure pain stimulation due to chemical activation of free nerve endings. During this interval, significant potentiation of Ib inhibition from GM to both Sol and Q motoneurones was observed. The time-course of these Ib heteronymous changes paralleled that of subjective pain sensation. These findings demonstrate that nociceptive discharge modifies the gain of Ib heteronymous effects in humans. Since the man function of these Ib pathways is to coordinate activity of muscles operating at different joints, it is suggested that nociceptive input may change muscle synergies by selecting specific subpopulations of Ib interneurones, thus contributing to establish appropriate adaptive motor strategies.     

Right sensory-motor syndrome as the presentation of a spontaneous cervico-thoracic epidural hematoma

INTRODUCTION: A spontaneous cervical epidural hematoma is an infrequent cause of cord compression. The commonest clinical presentations are with paraparesia and tetraparesia. Transient hemiparesia is very rare and a sensory-motor syndrome is exceptional. CLINICAL CASE: A 38 year old man had sudden onset of spontaneous interscapular vertebral pain with bilateral root radiation. A few minutes later he started to have weakness and sensory loss in his right limbs. On clinical examination there was pain on pressure over the spinal apophyses of the T4 and T5 vertebrae, hemiparesia and hemi-hypoalgesia of the right limbs. After ten hours this had all returned to normal. MRI of the cord showed an epidural hematoma extending from C6 to T2. Coagulation studies and spinal arteriography were normal. CONCLUSIONS: The sensory motor syndrome is an unusual form of presentation of a spontaneous cervico-thoracic epidural hematoma. Root pain is a symptom of great value for orientation of a syndrome which would otherwise seem to be of central origin. The explanation for this clinical findings may be compression of both lateral cord pathways due to their particular blood distribution. Regarding therapeutic approach, this should be conservative, with close observation to see whether it will resolve spontaneously in a short period of time.     

Toward a theory of pain: Relief of chronic pain by prefrontal leucotomy, opiates, placebos, and hypnosis.

Research concerned with the neurological correlates of the pain response and how this response can be mitigated or eliminated by various clinical procedures permit several tentative conclusions: (a) pain producing stimuli activate a variety of nerve fibers rather than activating specific "pain" nerve pathways. (b) Pain producing stimuli set off patterns of neural impulses which are different from those produced by other stimuli. (c) Discomfit due to pain is not necessarily present when the noxious stimulus has been discriminated. Discomfit can be eliminated by various clinical procedures without necessarily altering the sensation of pain. (d) Mitigation of discomfort by clinical procedures appears to be secondary to their more generalized effect, i.e., anxiety reduction. 174-item bibliog. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information.     

Scintigraphy of the lacrimal ducts

Scintigraphy of the lacrimal pathways is an examination method which informs us on the function of the efferent lacrimal system. The authors made bilateral scintigraphic examinations in 32 patients with obstruction or stenosis of the lacrimal pathways, 22 times they made concurrent contrast examinations of the lacrimal pathways. In seven suprasaccal and 5 saccal obstructions and stenoses they did not find penetration of activity from the conjunctival sac into the lacrimal pathways. In 16 subsaccal obstructions, 12 times penetration of activity into the lacrimal sac was found. In five patients with a partly preserved patency of the lacrimal pathways three times activity was detected in the lacrimal sac and in one instance slow penetration of activity into the nasal cavity. In complete obstructions and severe stenoses scintigraphy does not provide, as compared with conclusions of other examinations (fluorescein tests, irrigation, probing, contrast dacryocystography) new information on the type of obstruction. The method is useful in particular in conditions with a preserved patency of the lacrimal pathways, in examinations of very mild stenoses, intermittent lacrimation and doubtful cases. Scintigraphy of the lacrimal pathways is a supplementary method which must be evaluated in the context with other methods, in particular methods which provide information on the anatomy of the lacrimal system (dacryography).     

Pain associated with spinal cord injury

Management of pain after spinal cord injury remains a difficult clinical problem. In particular, neuropathic spinal cord injury pain, like other forms of deafferentation pain in which there is loss or modification of normal afferent sensory inputs, is notoriously resistant to currently available modes of treatment. Although there have been some advances in our understanding of spinal cord injury pain, the mechanisms of neuropathic spinal cord injury pain remain largely unknown and treatment is often ineffective. This review presents findings from recent publications that deal with the mechanisms and management of spinal cord injury pain.     

The induction of pain: an integrative review

The highly disagreeable sensation of pain results from an extraordinarily complex and interactive series of mechanisms integrated at all levels of the neuroaxis, from the periphery, via the dorsal horn to higher cerebral structures. Pain is usually elicited by the activation of specific nociceptors ('nociceptive pain'). However, it may also result from injury to sensory fibres, or from damage to the CNS itself ('neuropathic pain'). Although acute and subchronic, nociceptive pain fulfils a warning role, chronic and/or severe nociceptive and neuropathic pain is maladaptive. Recent years have seen a progressive unravelling of the neuroanatomical circuits and cellular mechanisms underlying the induction of pain. In addition to familiar inflammatory mediators, such as prostaglandins and bradykinin, potentially-important, pronociceptive roles have been proposed for a variety of 'exotic' species, including protons, ATP, cytokines, neurotrophins (growth factors) and nitric oxide. Further, both in the periphery and in the CNS, non-neuronal glial and immunecompetent cells have been shown to play a modulatory role in the response to inflammation and injury, and in processes modifying nociception. In the dorsal horn of the spinal cord, wherein the primary processing of nociceptive information occurs, N-methyl-D-aspartate receptors are activated by glutamate released from nocisponsive afferent fibres. Their activation plays a key role in the induction of neuronal sensitization, a process underlying prolonged painful states. In addition, upon peripheral nerve injury, a reduction of inhibitory interneurone tone in the dorsal horn exacerbates sensitized states and further enhance nociception. As concerns the transfer of nociceptive information to the brain, several pathways other than the classical spinothalamic tract are of importance: for example, the postsynaptic dorsal column pathway. In discussing the roles of supraspinal structures in pain sensation, differences between its 'discriminative-sensory' and 'affective-cognitive' dimensions should be emphasized. The purpose of the present article is to provide a global account of mechanisms involved in the induction of pain. Particular attention is focused on cellular aspects and on the consequences of peripheral nerve injury. In the first part of the review, neuronal pathways for the transmission of nociceptive information from peripheral nerve terminals to the dorsal horn, and therefrom to higher centres, are outlined. This neuronal framework is then exploited for a consideration of peripheral, spinal and supraspinal mechanisms involved in the induction of pain by stimulation of peripheral nociceptors, by peripheral nerve injury and by damage to the CNS itself. Finally, a hypothesis is forwarded that neurotrophins may play an important role in central, adaptive mechanisms modulating nociception. An improved understanding of the origins of pain should facilitate the development of novel strategies for its more effective treatment.     

Sensory and affective components of pain: Separation and synthesis.

It has become increasingly accepted that pain is not simply a sensation generated by nociceptors, but a perceptual phenomenon with particular emotional qualities. The purpose of this article is to bring together vastly different streams of research on the divisibility of pain into sensory and affective components. Empirical evidence for this divisibility is drawn from recent studies using multivariate statistics, signal detection theory, and unidimensional scaling. An important conclusion is that separable though pain components may be, they are not necessarily independent. In critiquing previous research, new criteria are derived for partitioning pain into sensory and affective components. Finally, speculations are offered as to how these same components might be synthesized on the basis of theories of perceptual organization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes. A possible pathway for discogenic low back pain

It has been thought that lumbar intervertebral discs were innervated segmentally. We have previously shown that the L5-L6 intervertebral disc in the rat is innervated bilaterally from the L1 and L2 dorsal root ganglia through the paravertebral sympathetic trunks, but the pathways between the disc and the paravertebral sympathetic trunks were unknown. We have now studied the spines of 17 rats to elucidate the exact pathways. We examined serial sections of the lumbar spine using immunohistochemistry for calcitonin gene-related peptide, a sensory nerve marker. We showed that these nerve fibres from the intervertebral disc ran through the sinuvertebral nerve into the rami communicantes, not into the corresponding segmental spinal nerve. In the rat, sensory information from the lumbar intervertebral discs is conducted through rami communicantes. If this innervation pattern applies to man, simple decompression of the corresponding nerve root will not relieve discogenic pain. Anterior interbody fusion, with the denervation of rami communicantes, may be effective for such low back pain.     

Pharmacotherapeutics in the management of orofacial pain

Pharmacotherapy is a cornerstone in the treatment of pain. Medications are often used to assist in diagnosis of the pain problem because positive or negative responses may delineate the cause of a particular pain. Through rational drug-prescribing habits and education of both patients and physicians, effective regimens can be designed to increase pain control while decreasing untoward drug side effects.     

Chronic pain and depression: Does the evidence support a relationship?

Examines the extent to which chronic pain and depression coexist by summarizing relevant literature and highlights common conceptual and methodological problems in this literature. The extent to which depression and chronic pain are associated remains a controversial issue that empirical studies have failed to resolve completely. An evaluation of relevant literature provides support for an association between the 2 syndromes and suggests that coexisting pain and depression may be a final common presentation reached by a number of potential pathways. Current biological, psychodynamic, and behavioral cognitive models of the mechanisms by which chronic pain and depression may interact are summarized. The literature suggests that a research approach is required to investigate the variety of paths by which individuals arrive at both chronic pain and depression. The usefulness of this strategy would be demonstrated if factors discriminating among subgroups of patients with both chronic pain and depression, and optimal intervention strategies for each, were determined. (2? p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pathophysiological mechanisms of central neuropathic pain after spinal cord injury

After spinal cord injury (SCI), between 10% and 20% of the patients may develop central neuropathic pain. This type of chronic pain usually is a very bothersome sequel and represents a major therapeutic challenge since conventional medical and surgical pain therapies generally are ineffective. This review focuses on recent advances in the understanding of the pathophysiology of this pain syndrome. Important clinical features of central neuropathic pain after SCI include loss of sensations mediated by spinothalamic pathways combined with development of abnormal pain perception (spontaneous continuous pain and abnormally evoked pain). Up-regulation of neuronal activity leading to spontaneous and evoked neuronal hyperactivity/hyperexcitability, may be the neurophysiological substrate for development of abnormal pain perception. This paper describes some neurochemical changes that may be important for the induction and maintenance of neuronal hyperactivity and abnormal pain perception: Increased excitatory glutaminergic activity involving N-methyl-D-aspartate (NMDA) receptor activation, may trigger the intracellular cascade reaction leading to upregulation of neuronal activity/excitability. Changes in voltage-sensitive Na+ channels may contribute to changes in nerve membrane excitability. Other important mechanisms may be loss of endogenous inhibition, including reduced gamma-amino-butyric acid (GABA)ergic, opioid and monoaminergic inhibition. These various mechanisms may provide new targets for treatment of a pain syndrome that traditionally has been so difficult to handle.     

Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms

This study, addressing etiologic and pathogenic aspects of fibromyalgia (FM), aimed at examining whether sensory abnormalities in FM patients are generalized or confined to areas with spontaneous pain. Ten female FM patients and 10 healthy, age-matched females participated. The patients were asked to rate the intensity of ongoing pain using a visual analogue scale (VAS) at the site of maximal pain, the homologous contralateral site and two homologous sites with no or minimal pain. Quantitative sensory testing was performed for assessment of perception thresholds in these four sites. Von Frey filaments were used to test low-threshold mechanoreceptive function. Pressure pain sensitivity was assessed with a pressure algometer and thermal sensitivity with a Thermotest. In addition the stimulus-response curve of pain intensity as a function of graded nociceptive heat stimulation was studied at the site of maximal pain and at the homologous contralateral site. FM patients had increased sensitivity to non-painful warmth (P < 0.01) over painful sites and a tendency to increased sensitivity to non-painful cold (P < 0.06) at all sites compared to controls, but there was no difference between groups regarding tactile perception thresholds. Compared to controls, patients demonstrated increased sensitivity to pressure pain (P < 0.001), cold pain (P < 0.001) and heat pain (P < 0.02) over all tested sites. The stimulus-response curve was parallely shifted to the left of the curve obtained from controls (P < 0.003). Intragroup comparisons showed that patients had increased sensitivity to pressure pain (P < 0.01) and light touch (P < 0.05) in the site of maximal pain compared to the homologous contralateral site. These findings could be explained in terms of sensitization of primary afferent pathways or as a dysfunction of endogenous systems modulating afferent activity. However, the generalized increase in sensitivity found in FM patients was unrelated to spontaneous pain and thus most likely due to a central nervous system (CNS) dysfunction. The additional hyperphenomena related to spontaneous pain are probably dependent on disinhibition/facilitation of nociceptive afferent input from normal (or ischemic) muscles.     

Review of Individuality in Pain and Suffering.

Reviews the book, Individuality in Pain and Suffering by Asenath Petrie (see record 1968-13362-000). One might expect from the title of this book that the author was going to supply the reader with new insights, or new theories, or new findings, or new ways of looking at the problems of pain and suffering. Instead it became increasingly obvious to the reviewer that the author is merely supplying us with new words for talking about the way people react to painful stimuli. Petrie's book is little involved (except for the reader) in pain and suffering. Her discussion of pain would probably require less than ten pages altogether. What the author appears to have done is written a book advocating her particular personality theory and reviewing all of the research that has been done relevant to that theory. This reviewer feels that, as far as any contribution to the literature on pain and suffering is concerned, the signal to noise ratio of this book does not match the price to usefulness ratio. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medullary catecholaminergic projections to the ventrolateral periaqueductal gray region activated by halothane anaesthesia

Under anaesthesia, blood loss and deep pain can evoke a premature, centrally-mediated sympathoinhibition leading to decompensated shock and sometimes even death. The central circuits evoking premature vasodepressor syncope are unknown, although medullary catecholaminergic pathways have been implicated. The ventrolateral periaqueductal gray region is one of only three brain regions in which catecholamine content is increased during halothane anaesthesia. The ventrolateral periaqueductal gray also contains neurons which are selectively activated by blood loss and deep pain, and recent work from our laboratory has suggested that it is a pivotal structure in central sympathoinhibitory circuits. Using retrograde tracing techniques combined with the immunohistochemical detection of: (i) the catecholamine synthetic enzyme, tyrosine hydroxylase and (ii) the protein product of the immediate-early gene c-fos as a marker of neuronal activation; the results of this study indicate that catecholaminergic projections from the A1, C1 and C2 regions of the medulla to the ventrolateral periaqueductal gray are activated by halothane anaesthesia. These data are consistent with the hypotheses that ascending catecholaminergic projections to the ventrolateral periaqueductal gray: (i) are a component of the central neural circuitry responsible for the sympathoinhibitory effects of halothane anaesthesia, and (ii) may contribute to the premature elicitation of vasodepressor syncope following blood loss and deep pain under conditions of anaesthesia.     

Cognitive-behavioral therapy for clinical pain control: a 15-year update and its relationship to hypnosis

Since Tan's (1982) review of cognitive and cognitive-behavioral methods for pain control was published 15 years ago, significant advances have been made in cognitive-behavioral therapy for pain. The scientific evidence for its efficacy for clinical pain attenuation is now much more substantial and is briefly reviewed. In particular, cognitive-behavioral therapy for chronic pain was recently listed as one of 25 empirically validated or supported psychological treatments available for various disorders. A number of emerging issues are further discussed in light of recent developments and research findings. The relationship of cognitive-behavioral therapy to hypnosis for pain control is briefly addressed, with suggestions for integrating hypnotic and cognitive-behavioral techniques.     

Neuroanatomy of the pain system and of the pathways that modulate pain

We review many of the recent findings concerning mechanisms and pathways for pain and its modulation, emphasizing sensitization and the modulation of nociceptors and of dorsal horn nociceptive neurons. We describe the organization of several ascending nociceptive pathways, including the spinothalamic, spinomesencephalic, spinoreticular, spinolimbic, spinocervical, and postsynaptic dorsal column pathways in some detail and discuss nociceptive processing in the thalamus and cerebral cortex. Structures involved in the descending analgesia systems, including the periaqueductal gray, locus ceruleus, and parabrachial area, nucleus raphe magnus, reticular formation, anterior pretectal nucleus, thalamus and cerebral cortex, and several components of the limbic system are described and the pathways and neurotransmitters utilized are mentioned. Finally, we speculate on possible fruitful lines of research that might lead to improvements in therapy for pain.     

Observational stress factors and musculoskeletal disorders in urban transit operators.

Associations and pathways between observed (rather than self-reported) job stressors and musculoskeletal disorders in 66 transit operators were investigated to determine specific stressors and vulnerable body regions affected, while adjusting for physical workload. Job stressors, defined as barriers to progress with work, comprised 7 categories and the sum of stressors. Outcomes included back and neck pain, low back pain, neck pain, pain of the upper extremities and the lower extremities, and any combination of these. Stressors were significantly associated with the combined musculoskeletal disorders category (odds ratio [OR] = 1.55), back and neck pain (OR = 1.41), low back pain (OR = 1.46), and pain in the lower extremities (OR = 1.44) after controlling for confounders. Five barrier categories had at least 1 significant association with outcomes. Results provide specific intervention targets by avoiding common method variance bias. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Abnormalities of mechanoreceptors in a rat model of neuropathic pain: possible involvement in mediating mechanical allodynia

1. Peripheral nerve injury sometimes leads to the development of neuropathic pain. One of the symptoms of such neuropathic pain is mechanical allodynia, pain in response to normally innocuous mechanical stimuli. We hypothesized that sympathetically driven dysfunction of cutaneous mechanoreceptors is responsible for signaling mechanical allodynia. The present study was undertaken to identify the types of sensory receptors that potentially mediate mechanical allodynia, with the use of a rat neuropathic pain model we have developed. 2. One week to 10 days after tight ligations of the L5 and L6 spinal nerves on one side, the rats fully developed behavioral signs of mechanical allodynia on the affected hindlimb. Various cutaneous mechanoreceptors originating from the neuropathic foot were examined by single-fiber recordings from the L4 dorsal root. 3. Although no particular abnormalities were found in other types of cutaneous mechanoreceptors, an unusual type of mechanoreceptor was found to be innervating the neuropathic foot. The response characteristics of this type of receptor resemble those of rapidly adapting mechanoreceptors (RAs), but with low and irregular static discharges during a maintained mechanical stimulus. We termed this unusual type as a "modified rapidly adapting" mechanoreceptor (MRA). 4. The response characteristics of MRAs change to those of typical RAs after a systemic injection of phentolamine, an alpha-adrenergic receptor blocker. 5. We conclude that many RAs become abnormal under the influence of sympathetic efferents in neuropathic pain, so that their response patterns change to those of MRAs. We propose that this abnormality is responsible for signaling the mechanical allodynia that can be seen in neuropathic pain states such as causalgia.