The peripheral L-arginine-nitric oxide-cyclic GMP pathway and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine on neuropathic pain in rats

Crotalphine, a 14 amino acid peptide first isolated from the venom of the South American rattlesnake Crotalus durissus terrificus, induces a peripheral long-lasting and opioid receptor-mediated antinociceptive effect in a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. In the present study, we further characterized the molecular mechanisms involved in this effect, determining the type of opioid receptor responsible for this effect and the involvement of the nitric oxide-cyclic GMP pathway and of K+ channels. Crotalphine (0.2 or 5 mu g/kg, orally; 0.0006 mu g/paw), administered on day 14 after nerve constriction, inhibited mechanical hyperalgesia and low-threshold mechanical allodynia. The effect of the peptide was antagonized by intraplantar administration of naltrindole, an antagonist of delta-opioid receptors, and partially reversed by norbinaltorphimine, an antagonist of kappa-opioid receptors. The effect of crotalphine was also blocked by 7-nitroindazole, an inhibitor of the neuronal nitric oxide synthase; by 1H-(1,2,4) oxadiazolo[4,3-a]quinoxaline-1-one, an inhibitor of guanylate cyclase activation; and by glibenclamide, an ATP-sensitive K+ channel blocker. The results suggest that peripheral delta-opioid and kappa-opioid receptors, the nitric oxide-cyclic GMP pathway, and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine. The present data point to the therapeutic potential of this peptide for the treatment of chronic neuropathic pain. Behavioural Pharmacology 23:14-24 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

A search for activation of C nociceptors by sympathetic fibers in complex regional pain syndrome

Although the term 'reflex sympathetic dystrophy' has been replaced by 'complex regional pain syndrome' (CRPS) type I, there remains a widespread presumption that the sympathetic nervous system is actively involved in mediating chronic neuropathic pain ["sympathetically maintained pain" (SMP)], even in the absence of detectable neuropathophysiology.

Sonographic visualization and ultrasound-guided block of the third occipital nerve: prospective for a new method to diagnose C2-C3 zygapophysial joint pain

BACKGROUND: Chronic neck pain after whiplash injury is caused by cervical zygapophysial joints in 50% of patients. Diagnostic blocks of nerves supplying the joints are performed using fluoroscopy. The authors' hypothesis was that the third occipital nerve can be visualized and blocked with use of an ultrasound-guided technique. METHODS: In 14 volunteers, the authors placed a needle ultrasound-guided to the third occipital nerve on both sides of the neck. They punctured caudal and perpendicular to the 14-MHz transducer. In 11 volunteers, 0.9 ml of either local anesthetic or normal saline was applied in a randomized, double-blind, crossover manner. Anesthesia was controlled in the corresponding skin area by pinprick and cold testing. The position of the needle was controlled by fluoroscopy. RESULTS: The third occipital nerve could be visualized in all subjects and showed a median diameter of 2.0 mm. Anesthesia was missing after local anesthetic in only one case. There was neither anesthesia nor hyposensitivity after any of the saline injections. The C2-C3 joint, in a transversal plane visualized as a convex density, was identified correctly by ultrasound in 27 of 28 cases, and 23 needles were placed correctly into the target zone. CONCLUSIONS: The third occipital nerve can be visualized and blocked with use of an ultrasound-guided technique. The needles were positioned accurately in 82% of cases as confirmed by fluoroscopy; the nerve was blocked in 90% of cases. Because ultrasound is the only available technique today to visualize this nerve, it seems to be a promising new method for block guidance instead of fluoroscopy.

[Chronic back ache--a psychosociobiological illness]

Chronic back pain is one of the eight most important symptoms of mankind in several lifetime prevalence studies. In the chronification process, an utmost important role is devoted to psychosocial influences, whereas structural abnormalities normally do not have a primal function in this process. The author also includes the discussion of the possibilities for the generalist to influence early the chronification process with the aim to keep the patient in his/her working environment.

[Therapy of disorders with central pain sensitization.]

Previous somatic pain experience (priming), psychobiographic imprinting (pain proneness), and stress (action proneness) are key to an enhanced centralised pain response. This centralised pain response clinically manifests itself in pain sensitization and chronification. The therapeutic approach to chronic centralised pain disorders is multimodal. The overarching aim of the various interventions of a multimodal treatment program is to activate anti-nociceptive areas of the cerebral matrix involved in pain processing. The lists of medications targeting neuropathic and somatoform pain disorder show considerable overlap. Psychotherapy helps patients with central pain sensitization to improve pain control, emotional regulation and pain behaviour.

Back pain in migrant farmworker families and farmworker high school students from Starr County, Texas

Back symptoms are a major global public health problem with the lifetime prevalence ranging between 50-80%. Research suggests that work-related factors contribute to the occurrence of back pain in various industries. Despite the hazardous nature, strenuous tasks, and awkward postures associated with farm work, little is known about back injury and symptoms in farmworker adults and children. Research in the United States is particularly limited. This is a concern given the large proportion of migrant farmworkers in the United States without adequate access to healthcare as well as a substantial number of youth working in agriculture. The present study describes back symptoms and identifies work-related factors associated with back pain in migrant farmworker families and farmworker high school students from Starr County, TX. Two separate datasets were used from two cohort studies "Injury and Illness Surveillance in Migrant Farmworkers (MANOS)" (study A: n=267 families) and "South Texas Adolescent Rural Research Study (STARRS)" (study B: n=345). Descriptive and inferential statistics including multivariable logistic regression were used to identify work-related factors associated with back pain in each study. In migrant farmworker families, the prevalence of chronic back pain during the last migration season ranged from 9.5% among youngest children to 33.3% among mothers. Chronic back pain was significantly associated with increasing age; fairly bad/very bad quality of sleep while migrating; fewer than eight hours of sleep at home in Starr County, TX; depressive symptoms while migrating; self-provided water for washing hands/drinking; weeding at work; and exposure to pesticide drift/direct spray. Among farmworker adolescents, the prevalence of severe back symptoms was 15.7%. Severe back symptoms were significantly associated with being female; history of a prior accident/back injury; feeling tense, stressed, or anxious sometimes/often; lifting/carrying heavy objects not at work; current tobacco use; increasing lifetime number of migrant farmworker years; working with/around knives; and working on corn crops. Overall, results support that associations between work-related exposures and chronic back pain and severe back symptoms remain after controlling for the effect of non-work exposures in farmworker populations. ^

Central pain augmentation in fibromyalgia during subjectively-matched mechanical stimulation

The precise pathophysiology of fibromyalgia, a syndrome characterized by, among other symptoms, chronic widespread pain, remains to be elucidated (Abeles et al., 2007). The fact that, when subjected to the same amount of stimulation, patients show enhanced brain responses as compared to controls provides evidence of central pain augmentation in this syndrome. We aimed to characterize brain response differences when stimulation is adjusted to elicit similar subjective levels of pain in both groups.

Pain and motor control of the lumbopelvic region: effect and possible mechanisms

Many authors report changes in the control of the trunk muscles in people with low back pain (LBP). Although there is considerable disagreement regarding the nature of these changes, we have consistently found differential effects on the deep intrinsic and superficial muscles of the lumbopelvic region. Two issues require consideration; first, the potential mechanisms for these changes in control, and secondly, the effect or outcome of changes in control for lumbopelvic function. Recent data indicate that experimentally induced pain may replicate some of the changes identified in people with LBP. While this does not exclude the possibility that changes in control of the trunk muscles may lead to pain, it does argue that, at least in some cases, pain may cause the changes in control. There are many possible mechanisms, including changes in excitability in the motor pathway, changes in the sensory system, and factors associated. with the attention demanding, stressful and fearful aspects of pain. A new hypothesis is presented regarding the outcome from differential effects of pain on the elements of the motor system. Taken together these data argue for strategies of prevention and rehabilitation of LBP (C) 2003 Elsevier Science Ltd. All rights reserved.

Evidence of altered lumbopelvic muscle recruitment in the presence of sacroiliac joint pain

Study Design. Cross-sectional study of electromyographic onsets of trunk and hip muscles in subjects with a clinical diagnosis of sacroiliac joint pain and matched control subjects. Objectives. To determine whether muscle activation of the supporting leg was different between control subjects and subjects with sacroiliac joint pain during hip flexion in standing. Background. Activation of the trunk and gluteal muscles stabilize the pelvis for load transference; however, the temporal pattern of muscle activation and the effect of pelvic pain on temporal parameters has not been investigated. Methods. Fourteen men with a clinical diagnosis of sacroiliac joint pain and healthy age-matched control subjects were studied. Surface electromyographic activity was recorded from seven trunk and hip muscles of the supporting leg during hip flexion in standing. Onset of muscle activity relative to initiation of the task was compared between groups and between limbs. Results. The onset of obliquus internus abdominis (OI) and multifidus occurred before initiation of weight transfer in the control subjects. the onset of obliquus internus abdominis, multifidus, and gluteus maximus was delayed on the symptomatic side in subjects with sacroiliac joint pain compared with control subjects, and the onset of biceps femoris electromyographic activity was earlier. IN addition, electromyographic onsets were different between the symptomatic and asymptomatic sides in subjects with sacroiliac joint pain. Conclusions. The delayed onset of obliquus internus abdominis, multifidus, and gluteus maximus electromyographic activity of the supporting leg during hip flexion, in subjects with sacroiliac joint pain. suggests an alteration in the strategy for lumbopelvic stabilization that may disrupt load transference through the pelvis.

Patients with neck pain demonstrate reduced electromyographic activity of the deep cervical flexor muscles during performance of the craniocervical flexion test

Study Design. Cross-sectional study. Objective. The present study compared activity of deep and superficial cervical flexor muscles and craniocervical flexion range of motion during a test of craniocervical flexion between 10 patients with chronic neck pain and 10 controls. Summary of Background Data. Individuals with chronic neck pain exhibit reduced performance on a test of craniocervical flexion, and training of this maneuver is effective in management of neck complaints. Although this test is hypothesized to reflect dysfunction of the deep cervical flexor muscles, this has not been tested. Methods. Deep cervical flexor electromyographic activity was recorded with custom electrodes inserted via the nose and fixed by suction to the posterior mucosa of the oropharynx. Surface electrodes were placed over the superficial neck muscles ( sternocleidomastoid and anterior scalene). Root mean square electromyographic amplitude and craniocervical flexion range of motion was measured during five incremental levels of craniocervical flexion in supine. Results. There was a strong linear relation between the electromyographic amplitude of the deep cervical flexor muscles and the incremental stages of the craniocervical flexion test for control and individuals with neck pain ( P = 0.002). However, the amplitude of deep cervical flexor electromyographic activity was less for the group with neck pain than controls, and this difference was significant for the higher increments of the task ( P < 0.05). Although not significant, there was a strong trend for greater sternocleidomastoid and anterior scalene electromyographic activity for the group with neck pain. Conclusions. These data confirm that reduced performance of the craniocervical flexion test is associated with dysfunction of the deep cervical flexor muscles and support the validity of this test for patients with neck pain.

Pain differs from non-painful attention-demanding or stressful tasks in its effect on postural control patterns of trunk muscles

Pain changes postural activation of the trunk muscles. The cause of these changes is not known but one possibility relates to the information processing requirements and the stressful nature of pain. This study investigated this possibility by evaluating electromyographic activity (EMG) of the deep and superficial trunk muscles associated with voluntary rapid arm movement. Data were collected from control trials, trials during low back pain (LBP) elicited by injection of hypertonic saline into the back muscles, trials during a non-painful attention-demanding task, and during the same task that was also stressful. Pain did not change the reaction time (RT) of the movement, had variable effects on RT of the superficial trunk muscles, but consistently increased RT of the deepest abdominal muscle. The effect of the attention-demanding task was opposite: increased RT of the movement and the superficial trunk muscles but no effect on RT of the deep trunk muscles. Thus, activation of the deep trunk muscles occurred earlier relative to the movement. When the attention-demanding task was made stressful, the RT of the movement and superficial trunk muscles was unchanged but the RT of the deep trunk muscles was increased. Thus, the temporal relationship between deep trunk muscle activation and arm movement was restored. This means that although postural activation of the deep trunk muscles is not affected when central nervous system resources are limited, it is delayed when the individual is also under stress. However, a non-painful attention-demanding task does not replicate the effect of pain on postural control of the trunk muscles even when the task is stressful.

Analysis of the acute postoperative pain experience following oral surgery: identification of 'unaffected', 'disabled' and 'depressed, anxious and disabled' patient clusters

Background: Pain is defined as both a sensory and an emotional experience. Acute postoperative tooth extraction pain is assessed and treated as a physiological (sensory) pain while chronic pain is a biopsychosocial problem. The purpose of this study was to assess whether psychological and social changes Occur in the acute pain state. Methods: A biopsychosocial pain questionnaire was completed by 438 subjects (165 males, 273 females) with acute postoperative pain at 24 hours following the surgical extraction of teeth and compared with 273 subjects (78 males, 195 females) with chronic orofacial pain. Statistical methods used a k-means cluster analysis. Results: Three clusters were identified in the acute pain group: 'unaffected', 'disabled' and 'depressed, anxious and disabled'. Psychosocial effects showed 24.8 per cent feeling 'distress/suffering' and 15.1 per cent 'sad and depressed'. Females reported higher pain intensity and more distress, depression and inadequate medication for pain relief (p

Glycine receptors: A new therapeutic target in pain pathways

Although glycine receptor Cl- channels (GlyRs) have long been known to mediate inhibitory neurotransmission onto spinal nociceptive neurons, their therapeutic potential for peripheral analgesia has received little attention. However, it has been shown that alpha 3-subunit-containing GlyRs are concentrated into regions of the spinal cord dorsal horn where nociceptive afferents terminate. Furthermore, inflammatory mediators specifically inhibit alpha 3-containing GlyRs, and deletion of the murine alpha 3 gene confers insensitivity to chronic inflammatory pain. This strongly implicates GlyRs in the inflammation-mediated disinhibition of centrally projecting nociceptive neurons. Future therapies aimed at specifically increasing current flux through alpha 3-containing GlyRs may prove effective in providing analgesia.

Unusual case of abdominal pain following liver transplant: causality or casualty?

This is an unusual case of chronic abdominal pain following two liver transplants with at least three potential causes: traumatic neuroma, intussusception of the small bowel of the Roux loop and biliary cast. Surgical removal of the latter two factors led to resolution of the pain. The management of the clinical case is discussed.