Conventional Analgesia Research Articles

Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain

Diabetic neuropathic pain remains an unmet clinical problem and is poorly relieved by conventional analgesics. N-methyl- d-aspartate (NMDA) receptors play an important role in central sensitization in neuropathic pain. Although NMDA antagonists are highly effective in reducing neuropathic pain, these agents cause severe side effects at therapeutic doses, which limit their clinical uses. Neramexane and memantine are uncompetitive NMDA antagonists with minimal side effects at therapeutic doses. Here we determined the antinociceptive effect of chronic administration of neramexane and compared its effect with that of memantine and gabapentin in a rat model of diabetic neuropathic pain. Mechanical hyperalgesia was measured with a noxious pressure stimulus, and tactile allodynia was assessed with von Frey filaments in diabetic rats induced by streptozotocin. Compared with vehicle-treated rats, treatment with neramexane (12.3, 24.6, and 49.2 mg/kg/day) for 2 weeks via an osmotic minipump produced dose-dependent and sustained effects on mechanical hyperalgesia and allodynia. Administration of memantine (20 mg/kg/day) or gabapentin (50 mg/kg/day) for 2 weeks also produced significant and persistent antinociceptive effects on mechanical hyperalgesia and allodynia. The magnitude of the antinociceptive effect produced by the intermediate and high doses of neramexane was comparable to that of gabapentin and memantine. The plasma level achieved by neramexane at 12.3, 24.6, and 49.2 mg/kg/day was 0.26 ± 0.04, 0.50 ± 0.05, and 1.21 ± 0.16 μM, respectively. These data suggest that neramexane at therapeutically relevant doses attenuates diabetic neuropathic pain. Our study provides valuable information about the therapeutic potential of chronic administration of neramexane and memantine for painful diabetic neuropathy.

Effects of adjunct electroacupuncture on severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease

To compare severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease treated with a combination of conventional analgesics and electroacupuncture (EAP) or with conventional analgesics alone. Controlled clinical trial. 15 dogs undergoing surgery because of acute thoracolumbar disk disease. Dogs were alternately assigned to treatment (conventional analgesics and adjunct EAP) and control (conventional analgesics alone) groups. Analgesic treatment was adjusted as necessary by the attending clinician, who was not aware of group assignment. Pain scores were assigned 1, 3, and 12 hours after surgery and every 12 hours thereafter for 72 hours by the same individual who performed acupuncture treatments. Total dose of fentanyl administered during the first 12 hours after surgery was significantly lower in the treatment group than in the control group, but dosages of analgesics administered from 12 through 72 hours after surgery did not differ between groups. Pain score was significantly lower in the treatment group than in the control group 36 hours after surgery, but did not differ significantly between groups at any other time. Results provided equivocal evidence that adjunct EAP might provide some mild benefit in regard to severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease.

Botulinum toxin for neuropathic pain?

Neurologists who routinely treat neuropathic pain are well aware that despite the plethora of pharmacologic agents that are purportedly effective in managing this difficult and complicated problem, the response to existing therapies is often inadequate. Neuropathic pain is often only partially responsive to conventional analgesics such as nonsteroidal anti-inflammatory drugs or opioids, which must be administered at relatively high doses, with a consequently high incidence of side effects. Fewer than 60% of patients obtain even partial relief from newer agents that have received regulatory approval for the treatment of neuropathic pain.1,2 Most of these treatments are also limited by their significant side effects. As a result, the search continues for newer treatments and additional novel therapeutic targets for what is still a largely unmet medical need. Sometimes, promising treatments arise from the application of established drugs to novel indications. A case in point is botulinum toxin. Botulinum toxin type A (BoNT/A) has been used for decades as the standard of care …

Adjuvant analgesics in neuropathic pain

Conventional analgesics have limited efficacy in the management of neuropathic pain. An adjuvant analgesic is a drug that has a primary nonpain indication but which may be analgesic in certain circumstances, and many of these have established a role in the pharmacological treatment of neuropathic pain. The number needed to treat is an indirect statistical measure that can be used to compare relative efficacy of different adjuvant analgesics and, from this, there is currently insufficient evidence to suggest that any one adjuvant analgesic has absolute advantages over another. Analgesic efficacy, tolerability, safety/toxicity, drug interactions, ease of use, and cost-effectiveness are essential factors that guide the selection of an adjuvant analgesic. Cost-effectiveness data are absent for the vast majority of these drugs. Pharmacological treatments should be used as part of a multimodal therapeutic programme for the management of neuropathic pain.

Clinical diagnosis and treatment of suspected neuropathic pain in three dogs

Three dogs were referred to The Queen's Veterinary School Hospital at University of Cambridge for chronic behavioural or locomotor disorders associated with pain. All three had been unsuccessfully treated with conventional analgesics, including non-steroidal anti-inflammatory drugs, glucocorticoids and opiate agonists, prior to referral, with minimal or no response. They were investigated by neurological examination plus conventional ancillary diagnostic tests and therapeutic drug trials. Ruling out other causes of pain and applying previously well-described criteria, each case was diagnosed as consistent with neuropathic pain, a poorly recognised condition in domestic dogs. Treatment with the tricyclic antidepressant drug, amitriptyline, or the antiepileptic drug, gabapentin, resulted in either a dramatic improvement or full resolution of clinical signs in all cases.

Effects of activation of group III metabotropic glutamate receptors on spinal synaptic transmission in a rat model of neuropathic pain

Chronic neuropathic pain remains an unmet clinical problem because it is often resistant to conventional analgesics. Metabotropic glutamate receptors (mGluRs) are involved in nociceptive processing at the spinal level, but their functions in neuropathic pain are not fully known. In this study, we investigated the role of group III mGluRs in the control of spinal excitatory and inhibitory synaptic transmission in a rat model of neuropathic pain induced by L5/L6 spinal nerve ligation. Whole-cell recording of lamina II neurons was performed in spinal cord slices from control and nerve-ligated rats. The baseline amplitude of glutamatergic EPSCs evoked from primary afferents was significantly larger in nerve-injured rats than in control rats. However, the baseline frequency of GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) was much lower in nerve-injured rats than in control rats. The group III mGluR agonist l(+)-2-amino-4-phosphonbutyric acid (l-AP4) produced a greater inhibition of the amplitude of monosynaptic and polysynaptic evoked EPSCs in nerve-injured rats than in control rats. l-AP4 inhibited the frequency of miniature EPSCs in 66.7% of neurons in control rats but its inhibitory effect was observed in all neurons tested in nerve-injured rats. Furthermore, l-AP4 similarly inhibited the frequency of GABAergic and glycinergic IPSCs in control and nerve-injured rats. Our study suggests that spinal nerve injury augments glutamatergic input from primary afferents but decreases GABAergic and glycinergic input to spinal dorsal horn neurons. Activation of group III mGluRs attenuates glutamatergic input from primary afferents in nerve-injured rats, which could explain the antinociceptive effect of group III mGluR agonists on neuropathic pain.

Semi-rigid thoracoscopy for undiagnosed exudative pleural effusions: a comparative study

Thoracoscopy is highly sensitive and accurate for detecting pleural effusions. However, most respiratory physicians are not familiar with the use of the more common rigid thoracoscope or the flexible bronchoscope, which is difficult to manipulate within the pleural cavity. The semi-rigid thoracoscope combines the best features of the flexible and rigid instruments. Since the practice with this instrument is limited in China, the diagnostic utility of semi-rigid thoracoscopy (namely medical thoracoscopy) under local anesthesia for undiagnosed exudative pleural effusions was evaluated. In 50 patients with undiagnosed pleural effusions who were studied retrospectively, 23 received routine examinations between July 2004 and June 2005 and the rest 27 patients underwent medical thoracoscopy during July 2005 and June 2006. Routine examinations of the pleural effusions involved biochemistry and cytology, sputum cytology, and thoracentesis. The difference in diagnostic sensitivity, costs related to pleural fluid examination and complications were compared directly between the two groups. Medical thoracoscopy revealed tuberculous pleurisy in 6 patients, adenocarcinoma in 7, squamous-cell carcinoma in 2, metastatic carcinoma in 3, mesothelioma in 2, non-Hodgkin's lymphoma in 1, and others in 4. Only 2 patients could not get definite diagnoses. Diagnostic efficiency of medical thoracoscopy was 93% (25/27). Only 21% patients were diagnosed after routine examinations, including parapneumonic effusion in 2 patients, lung cancer in 2 and undetermined metastatic malignancy in 1. Twelve patients with tuberculous pleurisy were suspected by routine examination. Costs related to pleural effusion testing showed no difference between the two groups (P=0.114). Twenty-three patients in the routine examination group underwent 97 times of thoracentesis. Two pleural infection patients and 2 pneumothorax patients were identified and received antibiotic treatment and drainage. Medical thoracoscopy could be well tolerated by all the patients. The semi-rigid thoracoscope could be easily controlled by chest physicians. The most common complication was transient chest pain (20 of 27 patients) from the indwelling chest tube, which would be managed with conventional analgesics. One case of subcutaneous emphysema and 2 cases of postoperative fever were self-limiting. No severe complications occurred. Medical thoracoscopy is a simple, safe, and cost-effective tool, with a high positive rate. Physicians should extend its access to proper patients if the facilities for medical thoracoscopy are available.

Orgasmic cephalgia: an uncommon presentation

Background: Orgasmic cephalgia is rare; but it is likely that its prevalence is underestimated because of patients\' arriere pensee when it comes to disclosing personal information concerning their sexual activities. Aim: To report a case of orgasmic cephalgia in a 34-year-old housewife. Method: All information was obtained from her medical records and investigation results. Relevant literature on headaches associated with sexual activity was also reviewed. Result: Patient developed sudden onset severe headache at orgasm, which rapidly worsened over 6 months to the extent that she began to dread all forms of sexual activity. She had only used unprescribed medication. She responded well to naratriptan and anxiolytics. By the third month of treatment, her headaches had completely disappeared. Conclusion: Most cases of orgasmic cephalgia are benign and probably do not require specific treatment. Triptans are useful for those that do not respond to conventional analgesics. Keywords : Headache, Orgasm, Sexual activity, Triptans Port Harcourt Medical Journal Vol. 2 (3) 2008: pp. 268-270

Fast-Track Anesthesia With Remifentanil and Spinal Analgesia for Cardiac Surgery: The Effect on Pain Control and Quality of Recovery

To assess pain intensity and quality of postoperative recovery in patients given fast-track anesthesia and spinal analgesia versus patients treated with standard anesthesia. A prospective, randomized, controlled study. A private institution. Eighty-three patients who underwent cardiac surgery with cardiopulmonary bypass were analyzed. General anesthesia consisted of remifentanil and spinal analgesia (low-dose morphine and clonidine) for the fast-track group (FTG) and sufentanil without spinal analgesia for the control group (CG). During the postoperative period, paracetamol and patient-controlled intravenous analgesia (PCA) with morphine were given. Postoperative pain intensity was evaluated during 48 hours with visual analog scale scores and intravenous morphine consumption. Pain impact on quality of life was assessed with the brief pain inventory (BPI) score (days 1-8), and recovery was evaluated with the quality of recovery score (QoR-40, day 4). Compared with the CG, FTG pain intensity was significantly lower 0 to 4 (p < 0.01) and 6 to 12 hours (p < 0.05) after surgery, as was their cumulative intravenous PCA morphine consumption (p = 0.01). BPI scores supported that FTG patients had significantly (p < 0.01) less "pain at its worst" on days 1 and 2, their BPI-assessed pain interfered significantly less with daily life on day 1 (p < 0.001), and their global QoR-40 score (day 4) was significantly higher (p < 0.05). Fast-track anesthesia combined with morphine-clonidine spinal analgesia controlled postoperative pain better and obtained a better QoR than conventional analgesia.

Primary care incidence and treatment of four neuropathic pain conditions: a descriptive study, 2002-2005.

BackgroundBetween 1992 and 2001 the UK general practice incidence of post-herpetic neuralgia and trigeminal neuralgia declined, whilst the incidence of painful diabetic neuropathy increased. The most common first line treatments were compound analgesics. As therapeutic options have subsequently changed, this study presents updated data on incidence and prescribing patterns in neuropathic pain.MethodsA descriptive analysis of the epidemiology and prescription treatment at diagnosis of incident post-herpetic neuralgia (n = 1,923); trigeminal neuralgia (1,862); phantom limb pain (57) and painful diabetic neuropathy (1,444) using computerised UK general practice records (THIN): May 2002 to July 2005.ResultsPrimary care incidences per 100,000 person years observation of 28 (95% confidence interval (CI) 27–30) for post-herpetic neuralgia, 27 (95%CI 26–29) for trigeminal neuralgia, 0.8 (95%CI 0.6–1.1) for phantom limb pain and 21 (95%CI 20–22) for painful diabetic neuropathy are reported. The most common initial treatments were tricyclic antidepressants (post-herpetic neuralgia) or antiepileptics (trigeminal neuralgia and painful diabetic neuropathy) and opioid analgesics (phantom limb pain). The mean number of changes before a stable drug regimen was 1.2 to 1.5 for trigeminal neuralgia, painful diabetic neuropathy and post-herpetic neuralgia, and 2.4 for phantom limb pain.ConclusionThe incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant. Despite more frequent use of antidepressants and antiepileptics for first line treatment, as opposed to conventional non-opioid analgesics, changes to therapy are common before a stable regimen is reached.

Spinal Antiallodynia Action of Glycine Transporter Inhibitors in Neuropathic Pain Models in Mice

Neuropathic pain is refractory against conventional analgesics, and thus novel medicaments are desired for the treatment. Glycinergic neurons are localized in specific brain regions, including the spinal cord, where they play an important role in the regulation of pain signal transduction. Glycine transporter (GlyT)1, present in glial cells, and GlyT2, located in neurons, play roles in modulating glycinergic neurotransmission by clearing synaptically released glycine or supplying glycine to the neurons and thus could modify pain signal transmission in the spinal cord. In this study, we demonstrated that i.v. or intrathecal administration of GlyT1 inhibitors, cis-N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-yl methyl)amino methylcarboxylic acid (ORG25935) or sarcosine, and GlyT2 inhibitors, 4-benzyloxy-3,5-dimethoxy-N-[1-(dimethylaminocyclopently)-methyl]benzamide (ORG25543) and (O-[(2-benzyloxyphenyl-3-fluorophenyl)methyl]-L-serine) (ALX1393), or knockdown of spinal GlyTs by small interfering RNA of GlyTs mRNA produced a profound antiallodynia effect in a partial peripheral nerve ligation model and other neuropathic pain models in mice. The antiallodynia effect is mediated through spinal glycine receptor alpha3. These results established GlyTs as the target molecules for the development of medicaments for neuropathic pain. However, these manipulations to stimulate glycinergic neuronal activity were without effect during the 4 days after nerve injury, whereas manipulations to inhibit glycinergic neuronal activity protected against the development of allodynia in this phase. The results implied that the timing of medication with their inhibitors should be considered, because glycinergic control of pain was reversed in the critical period of 3 to 4 days after surgery. This may also provide important information for understanding the underlying molecular mechanisms of the development of neuropathic pain.

Bilateral greater occipital nerve block for post‐dural puncture headache

Post-dural puncture headache (PDPH) is a frequent complication of procedures involving dural penetration for spinal anaesthesia, or following unintentional dural puncture during attempted epidural anaesthesia or analgesia. The International Headache Society has defined a PDPH as a bilateral headache that develops within 7 days and disappears within 14 days after the dural puncture. The headache worsens within 15 min of assuming an upright position and improves within 30 min of resuming the recumbent position [1]. The greater occipital nerve is formed by sensory fibres that originate in the C2 and C3 segments of the spinal cord. Its cutaneous sensory distribution extends over the posterior part of the head, spreading anteriorly to the vertex towards the area supplied by the ophthalmic division of the trigeminal nerve [2]. We present two cases of PDPH treated successfully with bilateral blockade of the greater occipital nerve. The first case was young healthy male who underwent surgery for umbilical herniorrhaphy. Spinal blockade was performed with a Whitacre 27 G needle. On the second postoperative day the patient complained of the typical symptoms of cervico-frontal PDPH. Conservative treatment was commenced with postural measures, hydration, caffeine and conventional analgesia. His symptoms did not improve and IV hydrocortisone was added the next day. Bilateral blockade of the greater occipital nerve was performed with bupivacaine 0.25% 4 ml and triamcinolone 20 mg. The headache completely disappeared a few minutes after the blockade. The patient was discharged on the fifth postoperative day. The second case was healthy young woman who developed a PDPH 40 h after accidental dural puncture during epidural blockade for labour analgesia. The catheter was left intrathecal during labour and after delivery we administered 0.9% saline 10 ml through the catheter. Conservative management, as in the first case, with IV hydrocortisone was started. The headache was accompanied by nausea and inability to breastfeed the baby, and we decided to perform a bilateral blockade of the greater occipital nerve with bupivacaine 0.25% and triamcinolone 20 mg. After the blockade, the symptoms improved significantly and the patient was able to resume normal activities. Forty-eight hours after performing the blockade, the patient was discharged home. Neither patient required further treatment after their discharge from hospital. PDPH is the result of the loss of cerebrospinal fluid lost through the dural tear into the epidural space. The headache is generally located in the frontal and occipital area, but may also involve the neck and upper shoulders [1, 3–5]. Many authors postulate that PDPH is caused by traction on pain-sensitive structures within the cranial cavity. However, there are no changes in the position of intracranial structures, suggesting that the traction theory does not fully explain the aetiology of the PDPH. Another hypothesis for PDPH is cerebral venous dilatation. The rationale for using greater occipital nerve block comes from the proximity of sensory neurons in the upper cervical spinal cord to the trigeminal nucleus caudalis (TNC) neurons and the convergence of sensory input to TNC neurons from both cervical and trigeminal fibres [2]. Blockade of the greater occipital nerve results in an interruption of pain from an area (the oculo-frontal area) where anaesthesia is not obtained [6, 7]. The greater occipital nerve only supplies the skin, muscles and vessels of the scalp [6]. The mechanism for the relief of the headache after blockade could be due to a ‘winding down’ of central sensitisation when afferent input to the dorsal horn and TNC is temporarily reduced [2]. Dorsal horn neurons at the C2 level respond to stimulation of both the dura mater and the greater occipital nerve. Moreover, stimulation of the greater occipital nerve facilitates C2 neuronal response to dural stimulation [2]. Greater occipital nerve block could, therefore, have a neuromodulatory effect on the central mechanism of the headache. Well-designed controlled studies are now needed to assess the role of greater occipital nerve block in the treatment of PDPH.

Does femoral nerve analgesia impact the development of postoperative delirium in the elderly? A retrospective investigation

Summary Background The potential effects of femoral nerve analgesia on postoperative delirium and length of stay remains poorly investigated. After detecting several cases of delirium in postoperative patients, we sought to find out if femoral nerve analgesia would prove superior in the prevention of postoperative delirium when compared to a conventional analgesia regimen. Methods Ninety-nine (99) patients were retrospectively investigated for delirium following hip fracture repair in 1 year (October 2004–October 2005). Patients were divided in two groups: Group 1 (n = 49) received patient-controlled femoral nerve analgesia (PCAF), Group 2 (n = 50) were treated with intravenous analgesia. All patients were studied for the following variables: age, gender, previous dementia, length of hospitalisation, blood transfusion, haemoglobin level at discharge, delirium, respiratory failure or oxygen therapy, heart failure or acute coronary disease, renal failure, stroke, rescue opioid analgesia, sitting and walking times, patients discharge to rehabilitation centre and patients discharge without walking recovery. Results Patients in Group 1 showed significantly less occurrence of postoperative delirium than those treated with conventional analgesia (8.2% and 42%, respectively). Patients in PCAF group did not receive any morphine rescue medication in contrast to 28% of those of Group 2 (p Conclusions The incidence of postoperative delirium was lower in the PCAF group. The PCAF technique in hip fracture repair improves the quality of postoperative analgesia, without needing rescue opioid analgesia.

Paravertebral analgesia for cardiac surgery

High-quality analgesia following cardiac surgery is infrequently obtained. Pain management is seldom a priority in the immediate postoperative care of these patients, who frequently require mechanical ventilation in an intensive care environment. These patients may be physiologically unstable, and attention to hemostasis and cardiopulmonary stability is usually of more concern in the initial phases of their care. Nevertheless, there are several compelling physiological, psychological, and humanitarian reasons that good pain relief should be offered to these patients. The frequently misguided perception that cardiac surgery is not painful, and the valid concerns many have regarding the side effects of opioid analgesia as well as the potential risks of thoracic epidural analgesia contribute to “oligoanalgesia” in the patient recovering from cardiac surgery. The evolution of minimally invasive cardiac surgery and the increasing clinical complexity of cardiac patients are providing an impetus to explore safe and effective analgesic techniques in this clinical domain. The role of paravertebral blockade in cardiac surgery has not been extensively investigated. At best, the literature to date is in the form of isolated case reports and observational studies. As such, a meaningful review of this topic can offer little more than commentary and discussion. However, paravertebral blockade has an established role in postoperative analgesia in general, and it confers some theoretical advantages over both conventional thoracic epidural analgesia as well as parenteral opioid therapy for cardiac patients.

Neuropathic changes in equine laminitis pain

Laminitis is a common debilitating disease in horses that involves painful disruption of the lamellar dermo-epidermal junction within the hoof. This condition is often refractory to conventional anti-inflammatory analgesia and results in unremitting pain, which in severe cases requires euthanasia. The mechanisms underlying pain in laminitis were investigated using quantification of behavioural pain indicators in conjunction with histological studies of peripheral nerves innervating the hoof. Laminitic horses displayed consistently altered or abnormal behaviours such as increased forelimb lifting and an increased proportion of time spent at the back of the box compared to normal horses. Electron micrographic analysis of the digital nerve of laminitic horses showed peripheral nerve morphology to be abnormal, as well as having reduced numbers of unmyelinated (43.2%) and myelinated fibers (34.6%) compared to normal horses. Sensory nerve cell bodies innervating the hoof, in cervical, C8 dorsal root ganglia (DRG), showed an upregulated expression of the neuronal injury marker, activating transcription factor-3 (ATF3) in both large NF-200-immunopositive neurons and small neurons that were either peripherin- or IB4-positive. A significantly increased expression of neuropeptide Y (NPY) was also observed in myelinated afferent neurons. These changes are similar to those reported in other neuropathic pain states and were not observed in the C4 DRG of laminitic horses, which is not associated with innervation of the forelimb. This study provides novel evidence for a neuropathic component to the chronic pain state associated with equine laminitis, indicating that anti-neuropathic analgesic treatment may well have a role in the management of this condition.

Involvement of neural cell adhesion molecule signaling in glial cell line-derived neurotrophic factor-induced analgesia in a rat model of neuropathic pain

Since neuropathic pain is resistant to conventional analgesics such as opiates and non-steroidal anti-inflammatory drugs, the development of new types of drugs for its treatment has been awaited. Several key molecules associated with nociception have been suggested as potential targets for new analgesics. Glial cell line-derived neurotrophic factor (GDNF) has a variety of functions affecting the survival and development of specified neural cell populations, mediated via transmission of intracellular signals through binding to its high-affinity receptor, GFRα1, and subsequent activation of a tyrosine receptor kinase, RET, neural cell adhesion molecule (NCAM), or other signaling molecules. GDNF also exhibits analgesic effects in rodent models of neuropathic pain, although the underlying mechanisms are still largely unknown, including the intracellular signal transduction involved. We report here that NCAM signaling plays a role in mediating the analgesic effect of GDNF in rats with chronic constrictive injury (CCI). We found that NCAM was expressed in intrinsic neurons in the spinal dorsal horn and in dorsal root ganglion neurons with small cell bodies. Reduction of NCAM expression by NCAM antisense oligodeoxynucleotide administration to CCI rats abolished the analgesic effect of GDNF without affecting RET signaling activation. An NCAM mimetic peptide, C3d, partially reduced the chronic pain induced by CCI. These findings suggest that NCAM signaling plays a critical role in the analgesic effect of GDNF and that development of new drugs activating GDNF–NCAM signaling may represent a new strategy for the relief of intractable pain.

Pre-Operative versus Postoperative Surgical Analgesia

Background; postoperative pain remain the most common dilemma for surgical patients, there are many&#x0D; methods for control of pain, either by conventional postoperative analgesia or preoperative analgesia.&#x0D; The aim; is to evaluate the benefit of Diclofenac as pre-operative analgesia in comparison to the&#x0D; postoperative conventional treatments.&#x0D; Methods and Patients; this study includes patients of different age and sex groups, underwent different&#x0D; elective and emergency surgical operations,&#x0D; They divided in to two groups:&#x0D; - Group A (100 patients): controlled group, were received pre-operative analgesia.&#x0D; - Group B (100 patients): compared group, were received the conventional analgesia.&#x0D; Results; thirty eight percent of patients in group A have significant pain versus eighty six percent of the&#x0D; patients in group B (P value 0.0000)&#x0D; Preoperative analgesia as single dose of Diclofenac is more effective in control of postoperative pain&#x0D; than conventional postoperative analgesia.&#x0D; Conclusion; we could say that the pre-operative (pre-emptive) analgesia is safe, feasible, well tolerant,&#x0D; less costly and more effective for the control of different types of the surgical pain.

Chinese Herbal Medicine for Cancer Pain

The purpose of this review is to summarize and evaluate the current status of clinical research on the use of Chinese herbal medicine in treating cancer pain, with emphasis on the efficacy and safety of the applications. A search of the clinical research published between 1986 and 2006 on the effects and applications of Chinese herbal medicine in cancer pain management was conducted using databases of CBM, CMCC, Wanfang, and Weipu (available since 1989) in Chinese and PubMed and EMBASE in English. We included only reports of original publications on cancer-induced pain, resulting in a total of 115 articles. We evaluated the methodological quality of the articles following the guidelines set forth as "Levels of Evidence of Human Studies of Cancer in Complementary and Alternative Medicine" by the National Cancer Institute. Various methods of traditional Chinese medicine herbal treatment for cancer pain management have been reported. These methods include external application, oral administration, intravenous infusion, and other applications such as inhalation and clysmata. Forty-one of the 115 studies reviewed were randomized controlled clinical trials, most comparing the effects of Chinese herbal medicine to conventional analgesics and the others using placebo controls. These trials suggest that (1) Chinese medicine may be effective for cancer pain, and its effects are similar to those of Western analgesics; (2) Chinese medicine may reduce the side effects of conventional analgesics, thus enhancing cancer patients' quality of life; and (3) the various methods of application--topical, oral, and intravenous--are suitable to treat a range of pain conditions found in cancer patients. However, trials were of varying quality with respect to control group selection, dosing and side effect information, and outcome measures. The studies reviewed in this article suggest that Chinese herbal medicine may be useful for managing cancer pain, at least for short-term application. The products evaluated appear relatively safe, with no serious adverse effects reported. However, the quality of the published reports is variable. More research using rigorously controlled clinical trial design is warranted.

Opioid analgesics in the management of neuropathic pain

Neuropathic pain affects 2 to 3% of the population in developed countries and can be particularly severe and debilitating. There has been considerable controversy regarding the role of opioid analgesics in the management of this disabling condition. However, a recent systematic review of high-quality randomized controlled trials (RCTs) utilizing opioid analgesics in the treatment of chronic neuropathic pain showed clinically significant benefit. These studies demonstrate, on average a 20 to 30% reduction in pain intensity. RCTs in patients with postherpetic neuralgia given controlled-release oxycodone or controlled-release morphine showed a significant reduction in pain intensity with variable improvement in sleep and disability. Trials of controlled-release oxycodone in painful diabetic neuropathy showed more consistent improvement in pain, sleep and ability to function. Nausea and constipation are common side effects, but can usually be controlled with anti-emetics and a bowel regimen, respectively. Psychological dependence or addiction is unusual in the absence of a history of substance abuse. Methadone may be particularly useful when conventional opioid analgesics have failed due to its N-methyl-D-aspartate (NMDA) antagonist properties. When antidepressants and anticonvulsants fail to provide adequate pain control for neuropathic pain, opioid analgesics are emerging as an important treatment option - in some cases, this class of drugs can make the difference between bearable and unbearable pain.

A synthetic kainoid, (2 S,3 R,4 R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1) serves as a novel anti-allodynic agent for neuropathic pain

In spite of prominent progress in basic pain research, neuropathic pain remains a significant medical problem, because it is often poorly relieved by conventional analgesics. Thus this situation encourages us to make more sophisticated efforts toward the discovery of new analgesics. We previously showed that i.t. administration of acromelic acid-A (ACRO-A), a Japanese mushroom poison, provoked prominent tactile pain (allodynia) at an extremely low dose of 1 fg/mouse. In the present study we synthesized ACRO-A analogues (2 S,3 R,4 R)-3-carboxymethyl-4-phenoxypyrrolidine-2-carboxylic acid (POPA-2) and (2 S,3 R,4 R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1) chemically and examined their ability to induce allodynia in conscious mice. Whereas POPA-2 induced allodynia at extremely low doses from 1 to 100 fg/mouse, similar to ACRO-A, PSPA-1 did not induce allodynia; rather, it inhibited the ACRO-A-induced allodynia with an ID 50 value (95% confidence limits) of 2.19 fg/mouse (0.04–31.8 fg/mouse). Furthermore, PSPA-1 relieved neuropathic pain produced by L5 spinal nerve transection on day 7 after the operation in a dose-dependent manner from 1 to 100 pg/mouse. In contrast, it did not affect thermal or mechanical nociception or inflammatory pain. PSPA-1 reduced the increase in neuronal nitric oxide synthase activity in the spinal cord of neuropathic pain mice assessed by NADPH-diaphorase histochemistry and blocked the allodynia induced by N-methyl- d-aspartate. These results demonstrate that PSPA-1 may represent a novel class of anti-allodynic agents for neuropathic pain acting by blocking the glutamate-nitric oxide pathway.