Jerzy Wordliczek

The effect of pentoxifiline on post-injury hyperalgesia in rats and postoperative pain in patients

Recent studies demonstrate that activation of proinflammatory cytokines following injury intensifies the process of nociception. The present investigation assessed the influence of pre-injury pentoxifiline (PTFL, a non-specific cytokine inhibitor) on the development of post-injury nociception in animals and patients. It was established that intrathecal or intraperitoneal PTFL, elevated the nociceptive threshold for mechanical stimuli in the formalin test in rats. Pre-injury PTFL also inhibited pain-related behaviour. These findings correlate with a lower TNFalpha level in the serum of animals receiving pre-injury PTFL. In clinical investigations PTFL was administered intravenously before elective cholecystectomy. Patients who received preoperative PTFL had lower opioid requirements in the early postoperative period than control. At the same time, serum levels of TNFalpha and IL6 were lower in the PTFL group. Our results confirm the hypothesis as to the possibility of modulating of nociception through preemptive administration of a cytokine inhibitor.

The Effects of Local Pentoxifylline and Propentofylline Treatment on Formalin-Induced Pain and Tumor Necrosis Factor- Messenger RNA Levels in the Inflamed Tissue of the Rat Paw

We sought to determine whether local administration of pentoxifylline (PTF) or propentofylline (PPTF), which hinders cytokine production, influences pain threshold and formalin-induced pain behavior in rats or the level of tumor necrosis factor-α (TNF-α) messenger RNA (mRNA) concentrations in the inflamed paw tissue. PTF (0.5, 1, or 2 mg) and PPTF (1 or 2 mg) injected intraplantarly (i.pl.) had no significant effect on pain threshold. Injection of 0.1 mL of a 12% formalin solution subcutaneously into the dorsal surface of the left hind-paw induced pain behavior (47.6 ± 4.6 incidents per 5 min), and PTF injected at doses of 1 and 2 mg/100 μ L i.pl. before (but not after) formalin was effective in antagonizing (33.6 ± 2.5 and 23.6 ± 3.4 incidents per 5 min, respectively) formalin-induced pain behavior. A similar antagonistic effect was observed after PPTF treatment at a dose of 2 mg/100 μ L; however, in contrast to PTF, at a later time point (85–90 min) after the formalin challenge, this effect was independent of the scheme of PPTF administration, before or after formalin. The effect of PTF on formalin-induced pain behavior did not parallel paw volume as measured by plethysmometer; however, PTF per se significantly increased the paw volume. Formalin injection significantly increased the TNF-α mRNA level in the inflamed tissue of the rat hind paw (150%). PTF administered before, but not after, formalin significantly antagonized (by approximately 40%) the observed increase in the level of TNF-α mRNA. Our study demonstrates and provides biochemical evidence that preemptive inhibition of proinflammatory cytokine synthesis by the use of PTF and PPTF, phosphodiesterase, and glial activation inhibitors is useful in antagonizing hyperalgesia in formalin-induced pain. Moreover, local administration of PTF may be a valuable approach to the treatment of inflammatory pain.

Diagnosis and management of neuropathic pain: review of literature and recommendations of the Polish Association for the study of pain and the Polish Neurological Society - part one.

Neuropathic pain may be caused by a variety of lesions or diseases of both the peripheral and central nervous system. The most common and best known syndromes of peripheral neuropathic pain are painful diabetic neuropathy, trigeminal and post-herpetic neuralgia, persistent post-operative and post-traumatic pain, complex regional pain syndrome, cancer-related neuropathic pain, HIV-related neuropathic pain and pain after amputation. The less common central pain comprises primarily central post-stroke pain, pain after spinal cord injury, central pain in Parkinson disease or in other neurodegenerative diseases, pain in syringomyelia and in multiple sclerosis. A multidisciplinary team of Polish experts, commissioned by the Polish Association for the Study of Pain and the Polish Neurological Society, has reviewed the literature on various types of neuropathic pain, with special focus on the available international guidelines, and has formulated recommendations on their diagnosis and treatment, in accordance with the principles of evidence-based medicine (EBM). High quality studies on the efficacy of various medicines and medical procedures in many neuropathic pain syndromes are scarce, which makes the recommendations less robust.

Peripheral opioid analgesia in laparoscopic cholecystectomy.

Background Recent research has revealed that opioids can act directly on the peripheral terminals of afferent nerves to mediate antinociception. The aim of this study was to assess the influence of peripheral morphine administration on the nociception process in the postoperative period. Methods One hundred fifty patients for laparoscopic cholecystectomy were randomly divided into 5 groups. Group M patients (n = 30) received local infiltration at trocar insertion points with 2 mg morphine in 20 mL of 0.9% NaCl solution (5 mL of solution per point) 10 minutes before the operation. For group B patients (n = 30), the solution used for infiltration was 20 mL of 0.25% bupivacaine; for group M+B patients (n = 30), the solution was 2 mg morphine in 20 mL of 0.25% bupivacaine; and for group S patients (n = 30), the solution was 20 mL 0.9% NaCl. For group S+M patients (n = 30), trocar insertion points were infiltrated with 20 mL of 0.9% NaCl, and patients in this group were given 2 mg of subcutaneous morphine 10 minutes before the surgery. Postoperative analgesic therapy was provided by on-demand analgesia with tramadol. After surgery, the following were measured: pain intensity scored on the visual analog scale, total tramadol requirement, time from the end of the surgical procedure to the administration of the first dose of tramadol, and the frequency of undesirable side effects (sedation, nausea, and vomiting). Results Pain intensity and total tramadol requirement after surgery were lower in groups M, B, and M+B compared with groups S and S+M, but these differences were not statistically significant. The time from the completion of the operation to the administration of the first dose of tramadol was significantly longer in groups M, B, and M+B compared with groups S and S+M. Conclusion Results of the study confirm the possibility of modifying the nociception process in the postoperative period through peripheral opioid administration.

Delivery systems of opioid analgesics for pain relief: a review.

Chronic pain is usually treated with pharmacological measures using opioids alone or in combination with adjuvant analgesics that play an important role in the treatment of pain not fully responsive to opioids administered alone, especially in neuropathic, bone and visceral colicky pain. The important part of the chronic pain treatment is the appropriate use of non-pharmacological measures along with psychosocial and spiritual support. Opioids may be administered by different routes; the most common and most convenient for majority of treated patients are oral and transdermal. However, in certain circumstances such as inability to swallow, lack of analgesic efficacy and intractable opioid-induced adverse effects parenteral routes (subcutaneous, intravenous) might be more useful. When these routes fail, in some patients intrathecal administration of opioids is required. Recently, more patients have been treated with short-acting opioids for breakthrough pain with sublingual, buccal and intranasal routes of opioid administration that may provide efficacy superior to oral and comparable to intravenous routes. Alternative routes comprise rectal, inhaled and topical administration of opioids. This article discusses various routes of opioid administration.

Intrathecal administration of doxepin attenuated development of formalin-induced pain in rats

Summary.The aim of the present research was to assess the influence of a tricyclic antidepressant doxepin administered intrathecally (i.t.) on the pain behavior in the formalin test (100 µl of 12% formalin was injected into the dorsal part of the hind paw under halotane anesthesia) in male Wistar rats. The influence of doxepin (62.5 µg i.t.) on the pain threshold and number of formalin-induced pain behaviors, as well as antinociceptive effect of morphine was studied. Doxepin significantly increased the nociceptive threshold in the paw pressure test, reduced formalin-induced pain behavior and potentiated morphine antinociceptive effect in formalin test. The obtained results indicate that analgesic effect of doxepin used before the injury is observable at the spinal level after intrathecal treatment, but not only after peripheral administration, which was shown in our previous study. The results of the present research demonstrated a possibility to modify the spinal nociceptive process by administration of doxepin before the formalin injection.

Transdermal and Topical Drug Administration in the Treatment of Pain

The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs) applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline) act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

Tapentadol – A representative of a new class of MOR-NRI analgesics

Tapentadol is a centrally acting analgesic with a dual mode of action as a μ-opioid receptor (MOR) agonist and a noradrenaline reuptake inhibitor (NRI). It was initially approved by the US Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients, and in August 2011, for chronic pain in an prolonged release form in the same population. Due to its limited protein binding capacity, the absence of active metabolites and significant microsomal enzyme induction or inhibition, tapentadol has a limited potential for drug-drug interactions. It appears to be well-tolerated and effective in the treatment of moderate-to severe acute and chronic pain. Owing to its dual mechanism of action, it is hypothesized to be good option in the treatment of both nociceptive and neuropathic pain.

Recommendations for assessment and management of pain in cancer patients

1Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan 2Department of Quality of Life Research, Medical University of Gdansk, Gdansk 3Department of Interdisciplinary Intensive Therapy, Jagiellonian University — Collegium Medicum in Krakow 4Department of Anaesthesiology and Intensive Therapy, Postgraduate Education Medical Centre in Warsaw 5Department of Palliative Care, Ludwik Rydygier Memorial, Collegium Medicum in Bydgoszcz 6Department of Pain Assessment and Management, Jagiellonian University — Collegium Medicum in Krakow 7Department of Palliative Care, Maria Sklodowska-Curie Institute — Oncology Center in Warsaw 8Department of Gastrointestinal Tract Cancers, Maria Sklodowska-Curie Institute — Oncology Center in Warsaw 9Department of Lungs and Thoracic Cancers, Maria Sklodowska-Curie Memorial Cancer Centre and Institute in Warsaw

Pharmacotherapy of pain in cancer patients– recommendations of the Polish Association for the Studyof Pain, Polish Society of Palliative Medicine, Polish Societyof Oncology, Polish Society of Family Medicine, and PolishSociety of Anaesthesiology and Intensive Therapy

Guidelines for the pharmacotherapy of pain in cancer patients were developed by a group of 21 experts of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, and Polish Society of Anaesthesiology and Intensive Therapy. During a series of meetings, the experts carried out an overview of the available literature on the treatment of pain in cancer patients, paying particular attention to systematic reviews and more recent randomized studies not included in the reviews. The search was performed in the EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials databases using such keywords as “pain”, “cancer”, “pharmacotherapy”, “analgesics”, and similar. The overviewed articles included studies of pathomechanisms of pain in cancer patients, methods for the assessment of pain in cancer patients, and drugs used in the pharmacotherapy of pain in cancer patients, including non-opioid analgesics (paracetamol, metamizole, non-steroidal anti-inflammatory drugs), opioids (strong and weak), coanalgesics (glucocorticosteroids, α2-adrenergic receptor agonists, NMDA receptor antagonists, antidepressants, anticonvulsants, topical medications) as well as drugs used to reduce the adverse effects of the analgesic treatment and symptoms other than pain in patients subjected to opioid treatment. The principles of opioid rotation and the management of patients with opioidophobia were discussed and recommendations for the management of opioid-induced hyperalgesia were presented. Drugs used in different types of pain experienced by cancer patients, including neuropathic pain, visceral pain, bone pain, and breakthrough pain, were included in the overview. Most common interactions of drugs used in the pharmacotherapy of pain in cancer patients as well as the principles for the pharmacotherapy of pain in cancer patients with organ dysfunctions (circulatory failure, chronic obstructive pulmonary disease,