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Journal Cover   ISRN Pain
  This is an Open Access Journal Open Access journal
   ISSN (Print) 2314-4718
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  • The Effect of Intravenous Lidocaine on Trigeminal Neuralgia: A Randomized
           Double Blind Placebo Controlled Trial

    • Abstract: Trigeminal neuralgia is the most common neuralgia. Its therapeutic approach is challenging as the first line treatment often does not help, or even causes intolerable side effects. The aim of our randomized double blind, placebo controlled, crossover study was to investigate in a prospective way the effect of lidocaine in patients with trigeminal neuralgia. Twenty patients met our inclusion criteria and completed the study. Each patient underwent four weekly sessions, two of which were with lidocaine (5 mgs/kg) and two with placebo infusions administered over 60 minutes. Intravenous lidocaine was superior regarding the reduction of the intensity of pain, the allodynia, and the hyperalgesia compared to placebo. Moreover, contrary to placebo, lidocaine managed to maintain its therapeutic results for the first 24 hours after intravenous infusion. Although, intravenous lidocaine is not a first line treatment, when first line medications fail to help, pain specialists may try it as an add-on treatment. This trial is registered with NCT01955967.
      PubDate: Mon, 10 Mar 2014 12:44:37 +000
  • Antinociceptive Effects of the Serotonin and Noradrenaline Reuptake
           Inhibitors Milnacipran and Duloxetine on Vincristine-Induced Neuropathic
           Pain Model in Mice

    • Abstract: Vincristine is an anticancer drug used to treat a variety of cancer types, but it frequently causes peripheral neuropathy. Neuropathic pain is often associated with the appearance of abnormal sensory signs, such as allodynia. Milnacipran and duloxetine, serotonin/noradrenaline reuptake inhibitors, have shown efficacy against several chronic pain syndromes. In this study, we investigated the attenuation of vincristine-induced mechanical allodynia in mice by milnacipran and duloxetine. To induce peripheral neuropathy, vincristine was administered once per day (0.1 mg/kg, intraperitoneally (i.p.)) for 7 days. Mechanical allodynia was evaluated by measuring the withdrawal response to stimulation with a von Frey filament. In vincristine-treated mice, mechanical allodynia was observed on days 3–28 of vincristine administration. A single administration of milnacipran (40 mg/kg, i.p.) or duloxetine (20 mg/kg, i.p.) had no effect on vincristine-induced mechanical allodynia. However, repeated administration of milnacipran (20 or 40 mg/kg, once per day, i.p.) or duloxetine (5, 10, or 20 mg/kg, once per day, i.p.) for 7 days significantly reduced vincristine-induced mechanical allodynia. These results suggest that chronic vincristine administration induces mechanical allodynia, and that repeated milnacipran and duloxetine administration may be an effective approach for the treatment of neuropathic pain caused by vincristine treatment for cancer.
      PubDate: Sun, 23 Feb 2014 15:38:21 +000
  • Distribution of Spinal Sensitization Evoked by Inflammatory Pain Using
           Local Spinal Cord Glucose Utilization Combined with 3H-Phorbol
           12,13-Dibutyrate Binding in Rats

    • Abstract: Aims. Hyperalgesia following tissue injury is induced by plasticity in neurotransmission. Few investigators have considered the ascending input which activates the superficial of spinal cord. The aim was to examine neurotransmission and nociceptive processing in the spinal cord after mustard-oil (MO) injection. Both in vitro and in vivo autoradiographs were employed for neuronal activity and transmission in discrete spinal cord regions using the 14C-2-deoxyglucose method and 3H-phorbol 12,13-dibutyrate (3H-PDBu) binding sites. Methods. To quantify the hyperalgesia evoked by MO, the flinching was counted for 60 min after MO (20%, 50 μL) injection in Wistar rats. Simultaneous determination of 14C-2-deoxyglucose and 3H-PDBu binding was used for a direct observation of neuronal/metabolic changes and intracellular signaling in the spinal cord. Results. MO injection evoked an increase in flinching for 60 min. LSCGU significantly increased in the Rexed I-II with 3H-PDBu binding in the ipsilateral side of spinal cord. Discussion. We clearly demonstrated that the hyperalgesia is primarily relevant to increased neuronal activation with PKC activation in the Rexed I-II of the spinal cord. In addition, functional changes such as “neuronal plasticity” may result in increased neuronal excitability and a central sensitization.
      PubDate: Thu, 26 Dec 2013 11:22:53 +000
  • A Health- and Resource-Oriented Perspective on NSLBP

    • Abstract: Nonspecific low back pain (NSLBP) is an important health issue of our time. Personal as well as economic factors, like suffering pain and experiencing disability on the one hand and enormous and still increasing costs to the economy and society on the other hand, display the importance of the matter. Tremendous research has been conducted in the last few decades on NSLBP. A PubMed search (June 17, 2013) on “low back pain” provided 22,980 hits, and when specifying for “low back pain, systematic review,” 3,134 hits were still generated. Most research has been done examining the development, risk factors, or therapeutic measures of NSLBP, but hardly any literature exists on resources related to NSLBP. The aims of this review are twofold. In order to shade light on the salutogenetic approach of NSLBP, and thus to focus on health instead of illness, the first aim is to facilitate the understanding of which therapeutic measures enhance the ability to cope with chronic NSLBP and enable (more) normal functioning in life. The second aim is to stimulate the understanding of resources protecting against the onset of NSLBP or against the development of chronic NSLBP and its resulting work absence.
      PubDate: Wed, 11 Sep 2013 11:19:51 +000
  • Tramadol Extended-Release for the Management of Pain due to Osteoarthritis

    • Abstract: Current knowledge on pathogenesis of osteoarticular pain, as well as the consequent several, especially on the gastrointestinal, renal, and cardiovascular systems, side effects of NSAIDs, makes it difficult to perform an optimal management of this mixed typology of pain. This is especially observable in elderly patients, the most frequently affected by osteoarthritis (OA). Tramadol is an analgesic drug, the action of which has a twofold action. It has a weak affinity to mu opioid receptors and, at the same time, can result in inhibition of the reuptake of noradrenaline and serotonin in nociceptorial descending inhibitory control system. These two mechanisms, “opioidergic” and “nonopioidergic,” are the grounds for contrasting certain types of pain that are generally less responsive to opioids, such as neuropathic pain or mixed OA pain. The extended-release formulation of tramadol has good efficacy and tolerability and acts through a dosing schedule that allows a high level of patients compliance to therapies with a good recovery outcome for the patients' functional status.
      PubDate: Wed, 04 Sep 2013 09:00:01 +000
  • PKC-Dependent Signaling Pathways within PAG and Thalamus Contribute to the
           Nitric Oxide-Induced Nociceptive Behavior

    • Abstract: Nitric oxide (NO) is an important molecule involved in nociceptive processing in the central nervous system. The release of NO within the spinal cord has long been implicated in the mechanisms underlying exaggerated pain sensitivity, and administration of NO donors can induce hyperalgesia. To elucidate the supraspinal mechanism responsible for NO-induced nociceptive hypersensitivity, we investigated the modulation of protein kinase C (PKC) and downstream effectors following treatment with the NO donors nitroglycerin and sodium nitroprusside. Both compounds induced a prolonged cold allodynia and heat hyperalgesia, increased levels of c-Fos and IL-1β, and activated NF-κB within periaqueductal grey matter and thalamus. Simultaneously, an increased expression and phosphorylation of PKC γ and ε were detected. To clarify the cellular mechanism involved in the NO-induced hypernociception, we examined the expression of transcription factors that act as PKC downstream effectors. A dramatic hyperphosphorylation of CREB and STAT1 was observed. The i.c.v. administration of the PKC blocker calphostin C prevented the NO-induced hypernociception, the hyperphosphorylation of CREB and STAT1, and partially reduced NF-κB activation. Conversely, the increase of IL-1β was unmodified by calphostin C. These results suggest the relevance of cerebral PKC-mediated CREB and STAT1 activation in the NO donor-induced nociceptive behavior.
      PubDate: Wed, 21 Aug 2013 11:17:40 +000
  • Double-Blind Acupuncture Needle: A Potential Tool to Investigate the
           Nature of Pain and Pleasure

    • Abstract: Background. Most of our knowledge about similarities in the neural processing of painful and pleasant sensations in the brain derives from studying each phenomenon separately. Patients often feel pain induced by acupuncture, which is noxious stimulation having the symbolic message of the cure, as pleasant. Objectives. We investigated whether the double-blind acupuncture needles are a potential tool to investigate coinciding pain and pleasant events. Methods. Participants were 109 healthy acupuncture students. An acupuncturist applied the double-blind placebo and the matching penetrating needle at bilateral forearm of each subject, one needle on each side of the arm. We asked the subjects to rate the pain associated with needle application and its unpleasantness or pleasantness on a visual analogue scale. Results. Of 65 penetrating needle applications that elicited pain, 29 (45%) subjects did not describe the pain as being unpleasant, and interestingly, 18 (28%) subjects described the needle insertion as pleasant. There was no significant difference in reported pain intensity between penetrating needles elicited pain that elicited a pleasant sensation and those that elicited an unpleasant sensation (). Conclusions. The double-blind acupuncture needles can be a potential tool for investigating the concomitant hedonic (pleasure) experience of pain.
      PubDate: Sun, 18 Aug 2013 11:07:59 +000
  • Changes in the Bispectral Index in Response to Experimental Noxious
           Stimuli in Adults under General Anesthesia

    • Abstract: Objective. Pain assessment is a major challenge in nonverbal patients in the intensive care unit (ICU). Recent studies suggest a relationship between the Bispectral Index (BIS) and nociceptive stimuli. This study was designed to examine changes in BIS in response to experimental noxious stimuli. Methods. Thirty participants under general anesthesia were in this quasiexperimental, within subject, pre- and poststudy. In the operating room (OR), BIS was monitored during moderate and severe noxious stimuli, induced by a thermal probe on the participants’ forearm, after induction of general anesthesia, prior to surgery. Results. Significant increases in BIS occurred during moderate (increase from 35.00 to 40.00, ) and severe noxious stimuli (increase from 37.67 to 40.00, ). ROC showed a sensitivity (Se) of 40.0% and a specificity (Sp) of 73.3% at a BIS value > 45, in distinguishing a moderate from a severe noxious stimuli. Conclusion. BIS increased in response to moderate and severe noxious stimuli. The Se and Sp of the BIS did not support the use of the BIS for distinction of different pain intensities in the context of deep sedation in the OR. However, the results justify further studies in more lightly sedated patients such as those in the ICU.
      PubDate: Thu, 01 Aug 2013 08:31:32 +000
  • Neural Mechanisms That Underlie Angina-Induced Referred Pain in the
           Trigeminal Nerve Territory: A c-Fos Study in Rats

    • Abstract: The present study was designed to determine whether the trigeminal sensory nuclear complex (TSNC) is involved in angina-induced referred pain in the trigeminal nerve territory and to identify the peripheral nerve conducting nociceptive signals that are input into the TSNC. Following application of the pain producing substance (PPS) infusion, the number of Fos-labeled cells increased significantly in the subnucleus caudalis (Sp5C) compared with other nuclei in the TSNC. The Fos-labeled cells in the Sp5C disappeared when the left and right cervical vagus nerves were sectioned. Lesion of the C1-C2 spinal segments did not reduce the number of Fos-labeled cells. These results suggest that the nociceptive signals that conduct vagal afferent fibers from the cardiac region are input into the Sp5C and then projected to the thalamus.
      PubDate: Sun, 28 Jul 2013 13:57:13 +000
  • Opioid Mechanism Involvement in the Synergism Produced by the Combination
           of Diclofenac and Caffeine in the Formalin Model

    • Abstract: Analgesics can be administered in combination with caffeine for improved analgesic effectiveness in a process known as synergism. The mechanisms by which these combinations produce synergism are not yet fully understood. The aim of this study was to analyze whether the administration of diclofenac combined with caffeine produced antinociceptive synergism and whether opioid mechanisms played a role in this event. The formalin model was used to evaluate the antinociception produced by the oral administration of diclofenac, caffeine, or their combination. Opioid involvement was analyzed through intracerebroventricular (i.c.v.) administration of naloxone followed by the oral administration of the study drugs. Diclofenac presented a dose-dependent effect, with a mean effective dose (ED50) of 6.7 mg/kg. Caffeine presented an analgesic effect with a 17–36% range. The combination of subeffective doses of each of the two drugs presented the greatest synergism with an effect of 57.7 ± 5.6%. The maximal antinociceptive effect was obtained with the combination of 10.0 mg/kg diclofenac and 1.0 mg/kg of caffeine, with an effect of 76.7 ± 5.6%. The i.c.v. administration of naloxone inhibited the effect of diclofenac, both separately and combined. In conclusion, caffeine produces antinociceptive synergism when administered in combination with diclofenac, and this synergism is partially mediated by opioid mechanisms at the central level.
      PubDate: Thu, 09 May 2013 14:30:28 +000
  • Evidence of Physiotherapy Interventions for Patients with Chronic Neck
           Pain: A Systematic Review of Randomised Controlled Trials

    • Abstract: Chronic neck pain (CNP) is common and costly, and the effect of physiotherapeutic interventions on the condition is unclear. We reviewed the literature for evidence of effect of physiotherapy interventions on patients with CNP. Five bibliographic databases (MEDLINE, EMBASE, CINAHL, Cochrane Library, and PEDro) were systematically searched. Randomised, placebo and active-treatment-controlled trials including physiotherapy interventions for adults with CNP were selected. Data were extracted primary outcome was pain. Risk of bias was appraised. Effect of an intervention was assessed, weighted to risk of bias. 42 trials reporting on randomised comparisons of various physiotherapy interventions and control conditions were eligible for inclusion involving 3919 patients with CNP. Out of these, 23 were unclear or at high risk of bias, and their results were considered moderate- or low-quality evidence. Nineteen were at low risk of bias, and here eight trials found effect on pain of a physiotherapy intervention. Only exercise therapy, focusing on strength and endurance training, and multimodal physiotherapy, cognitive-behavioural interventions, massage, manipulations, laser therapy, and to some extent also TNS appear to have an effect on CNP. However, sufficient evidence for application of a specific physiotherapy modality or aiming at a specific patient subgroup is not available.
      PubDate: Mon, 15 Apr 2013 16:25:52 +000
  • Duration of Analgesia Induced by Acupuncture-Like TENS on Experimental
           Heat Pain

    • Abstract: Background. Acupuncture-like TENS (AL-TENS) is a treatment modality that can be used to temporarily reduce pain. However, there is no clear data in the literature regarding the specific duration of analgesia induced by AL-TENS. Objectives. To describe and quantify the duration and magnitude of AL-TENS analgesia on experimental heat pain in healthy subjects and verify if the duration or magnitude of analgesia induced by the AL-TENS was influenced by the duration of the application of the AL-TENS (15 versus 30 minutes). Methods. A repeated-measures, intrasubject randomized experimental design was used, where each participant was his/her own control. 22 healthy volunteers underwent heat pain stimulations with a contact thermode before (pretest) and after (posttest) AL-TENS application (15 and 30 minutes). Outcome measures included subjective pain during AL-TENS, duration, and magnitude of AL-TENS-induced analgesia. Results. Survival analysis showed that the median duration of AL-TENS analgesia was 10 minutes following the application of either 15 or 30 minutes of AL-TENS. The magnitude of analgesia following either application was comparable at all points in time ( values > 0.05) and ranged between −20% and −36% pain reduction. Conclusion. Only half of the participants still had heat-pain analgesia induced by the AL-TENS at 15 minutes postapplication.
      PubDate: Sun, 07 Apr 2013 16:17:06 +000
  • Electrophysiological Study of the Antinociception Produced by the
           Coapplication of (±)-CPP and Propentofylline in Monoarthritic Rats

    • Abstract: The NMDA receptor is central in the generation and maintenance of chronic pain. This receptor has several sites of modulation. One is the glutamate recognition site that can be blocked by (±)-3-(2-carboxypiperazin-yl)propyl-1-phosphoric acid or (±)-CPP. We investigated whether the effect of glial inhibition produced by propentophylline (PPF) can be enhanced when combined with (±)-CPP. We used Sprague-Dawley rats with experimental monoarthritis, administering intrathecally the ED30 for both drugs (3.97 μg of (±)-CPP and 1.42 μg of PPF), since this combination produces an antinociceptive supra-additive effect when used in mechanical nociception (Randall-Selitto test). The combination of (±)-PPF and CPP produced an antinociceptive effect which was greater than that each drug alone as tested by both the C reflex and windup. We conclude that the antinociceptive effect of the combination of (±)-PPF and CPP possibly generates a supra additive interaction type in monoarthritic rats.
      PubDate: Thu, 04 Apr 2013 08:12:31 +000
  • Flexion Relaxation Ratio Not Responsive to Acutely Induced Low Back Pain
           from a Delayed Onset Muscle Soreness Protocol

    • Abstract: Background. The flexion relaxation ratio (FRR) has been suggested as a measure of muscular performance in patients with low back pain (LBP). The purpose of this study was to investigate whether the FRR was responsive to acute LBP produced from a delayed onset muscle soreness (DOMS) protocol. Methods. Fifty-one pain-free volunteers performed DOMS to induce LBP. Current pain intensity, trunk flexion range of motion (ROM), and passive straight leg raise (SLR) were measured at baseline, 24 and 48 hours after DOMS. Participants were categorized into pain groups based on reported current pain intensity. Changes in FRR, trunk flexion ROM, and SLR ROM were examined using two-way repeated measures analysis of variance. Results. Pain group was not found to have a significant effect on FRR ( = 0.054, ), nor were there any two-way interactions for changes in FRR. The pain group had decreased trunk flexion ROM compared to the minimal pain group ( = 7.21, ), but no decreases in SLR ROM ( = 3.51, ) over time. Interpretation. There were no differences in FRR based on reported pain intensity of LBP from a DOMS protocol. The responsiveness of FRR might be limited in patients with acute onset LBP of muscular origin.
      PubDate: Mon, 25 Feb 2013 14:00:02 +000
  • Characterization of the Visceral Antinociceptive Effect of Glial Glutamate
           Transporter GLT-1 Upregulation by Ceftriaxone

    • Abstract: Recent studies demonstrate that glial glutamate transporter-1 (GLT-1) upregulation attenuates visceral nociception. The present work further characterized the effect of ceftriaxone- (CTX-) mediated GLT-1 upregulation on visceral hyperalgesia. Intrathecal pretreatment with dihydrokainate, a selective GLT-1 antagonist, produced a reversal of the antinociceptive response to bladder distension produced by CTX. The hyperalgesic response to urinary bladder distension caused by intravesicular acrolein was also attenuated by CTX treatment as was the enhanced time spent licking of abdominal area due to intravesicular acrolein. Bladder inflammation via cyclophosphamide injections enhanced the nociceptive to bladder distension; cohorts administered CTX and concomitant cyclophosphamide showed reduced hyperalgesic response. Cyclophosphamide-induced bladder hyperalgesia correlated with a significant 22% increase in GluR1 AMPA receptor subunit expression in the membrane fraction of the lumbosacral spinal cord, which was attenuated by CTX coadministration. Finally, neonatal colon insult-induced hyperalgesia caused by intracolonic mustard oil (2%) administration at P9 and P11 was attenuated by CTX. These studies suggest that GLT-1 upregulation (1) attenuates the hyperalgesia caused by bladder irritation/inflammation or by neonatal colonic insult, (2) acts at a spinal site, and (3) may produce antinociceptive effects by attenuating GluR1 membrane trafficking. These findings support further consideration of this FDA-approved drug to treat chronic pelvic pain syndromes.
      PubDate: Tue, 25 Dec 2012 18:21:34 +000
  • Depression, Depressive Somatic or Nonsomatic Symptoms, and Function in a
           Primarily Hispanic Chronic Pain Population

    • Abstract: Chronic pain and depression are two major causes of disability. Comorbidity decreases psychosocial and physical functioning while increasing economic burden. The prevailing belief that Hispanics somaticize depression may hinder the diagnostic process and, thus, may impact outcomes. The purpose of this study was to explore the relationships among depression and depressive symptoms (somatic or nonsomatic) and function in chronic pain sufferers residing along the USA-Mexico border. Like other studies, as level of depression increased, level of pain increased and level of functioning decreased. So much so that almost a quarter of the participants reported moderate-to-severe depression, and another quarter of the participants reported suicidal ideation independent of depression or treatment. Unlike other published reports, we used a sample of chronic pain patients who received individualized, multimodal pain treatment. Compared to our previous work in a similar population, pain intensity and suicidal ideation were lower in this study. A plausible explanation is the use of antidepressants as adjuvant treatment for pain. Regardless of gender or ethnicity, persons with chronic pain will disclose symptoms of depression when appropriate tools are used to collect the data. Implications for future research and clinical practice are discussed.
      PubDate: Sat, 01 Dec 2012 11:10:43 +000
  • Intravenous Methadone for Severe Cancer Pain: A Presentation of 10 Cases

    • Abstract: Purpose. Methadone, a synthetic opioid agonist, is an effective alternative to strong opioids (morphine, hydromorphone, oxycodone, and buprenorphine) and is widely available as an oral formulation. Few data have been published so far on the use of intravenous (i.v.) methadone for the management of severe or refractory cancer pain. Methods. We followed 10 consecutives cancer patients with severe pain, treated with IV methadone. All had advanced disease and had already received strong opioids, some in association with ketamine. Pain was assessed at T0, T24 hours, and at the end of the treatment. Results. All patients benefited from the switch to IV methadone with a reduction of pain on VAS after 24 hours (median: 4/10; range 0–5) until the end of the treatment (all cases <3/10). The median starting dose was 100 mg/day (range 20–400) and the final dose remained stable with a median of 100 mg/day (range 27–700). The median duration of IV methadone was 11 days (range 2–59). No cardiac toxicity had been observed. Conclusions. IV methadone is an effective pain relieving alternative for the treatment of severe cancer pain, especially in refractory pain syndrome. Moreover, we did not observe any toxicity (neurological or cardiac) or any other major side effects and the treatment was overall well tolerated. More extensive comparative studies should be planned.
      PubDate: Wed, 28 Nov 2012 19:08:02 +000
  • Time Course of Placebo Effect of Acupuncture on Pain: A Systematic Review

    • Abstract: Objectives. Our objective was to investigate the time course of the placebo effect of acupuncture on pain and the factors affecting the placebo effect. Methods. Previously we retrieved three-armed randomized acupuncture trials including sham and no-treatment groups which were published until October 2009. We searched electronic databases again to identify additional trials from October 2009 to December 2011. After a screening of trials, fifteen three-armed acupuncture trials for pain were included in the analysis. Standardized mean differences between the sham and no-treatment groups were calculated for placebo effect. We then plotted the magnitude of the placebo effect over time. Results. The placebo effect gradually has increased for 12 weeks with a standardized mean difference of 0.74 (95% CI: 0.54 to 0.94). Then it decreased after 12 weeks as time passed. When the placebo effects were compared for factors including methodological qualities, they were not affected by all factors, except patient blinding. Trials with sufficient patient blinding showed a larger placebo effect at 8 weeks than those with insufficient patient blinding (). Conclusion. The placebo effect of acupuncture showed a unique pattern, which was affected by insufficient patient blinding.
      PubDate: Wed, 28 Nov 2012 09:52:59 +000
  • Complementary and Alternative Medicine in the Treatment of Chronic Pelvic
           Pain in Women: What Is the Evidence'

    • Abstract: Chronic pelvic pain (CPP) is defined as pain of at least 6 months’ duration that occurs in the lower abdomen or below the umbilicus and has resulted in functional or psychological disability or required intervention and treatment. Therapeutic interventions center around the treatment of CPP as a diagnosis in and of itself, and treatment of specific disorders that may be related to CPP. A multidisciplinary approach for diagnosis and treatment seems to be most effective for symptomatic relief. This paper reviews the evidence for such interventions as psychological treatments including the use of complementary and alternative medicine techniques for CPP in women. Unfortunately, finding the best evidence in this setting is difficult as only very few randomized controlled trials are available. A combination of treatments is usually required over time for the treatment of refractory CPP. The multifactorial nature of CPP needs to be discussed with the patient and a good rapport as well as a partnership needs to be developed to plan a management program with regular followup. Promotion of a multidisciplinary approach which includes complementary and alternative medicine techniques in managing CPP in women seems to yield the best results.
      PubDate: Wed, 28 Nov 2012 09:12:17 +000
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