The importance of chemokines in neuropathic pain development and opioid analgesic potency

Neuropathic pain is a serious clinical issue, and its treatment remains a challenge in contemporary medicine. Thus, dynamic development in the area of animal and clinical studies has been observed. The mechanisms of neuropathic pain are still not fully understood; therefore, studies investigating these mechanisms are extremely important. However, much evidence indicates that changes in the activation and infiltration of immune cells cause the release of pronociceptive cytokines and contribute to neuropathic pain development and maintenance. Moreover, these changes are associated with low efficacy of opioids used to treat neuropathy. To date, the role of CC chemokine receptor type 3 (CCR3) in nociception has not been studied. Similarly, little is known about its endogenous ligands (C-C motif ligand; CCL), namely, CCL5, CCL7, CCL11, CCL24, CCL26, and CCL28. Our research showed that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with upregulation of CCL7 and CCL11 in the spinal cord and dorsal root ganglia (DRG). Moreover, our results provide the first evidence that single and repeated intrathecal administration of the CCR3 antagonist SB328437 diminishes mechanical and thermal hypersensitivity. Additionally, repeated administration enhances the analgesic properties of morphine and buprenorphine following nerve injury. Simultaneously, the injection of SB328437 reduces the protein levels of some pronociceptive cytokines, such as IL-6, CCL7, and CCL11, in parallel with a reduction in the activation and influx of GFAP-, CD4- and MPO-positive cells in the spinal cord and/or DRG. Moreover, we have shown for the first time that an inhibitor of myeloperoxidase-4-aminobenzoic hydrazide may relieve pain and simultaneously enhance morphine and buprenorphine efficacy. The obtained results indicate the important role of CCR3 and its modulation in neuropathic pain treatment and suggest that it represents an interesting target for future investigations.

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CCR4 antagonist (C021) influences the level of nociceptive factors and enhances the analgesic potency of morphine in a rat model of neuropathic pain

European Journal of Pharmacology ◽

10.1016/j.ejphar.2020.173166 ◽

2020 ◽

Vol 880 ◽

pp. 173166 ◽

Cited By ~ 2

Author(s):

Joanna Bogacka ◽

Katarzyna Popiolek-Barczyk ◽

Katarzyna Pawlik ◽

Agata Ciechanowska ◽

Wioletta Makuch ◽

...

Keyword(s):

Neuropathic Pain ◽

Rat Model ◽

Analgesic Potency

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Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain

Pharmacological Reports ◽

10.1007/s43440-020-00137-8 ◽

2020 ◽

Vol 72 (5) ◽

pp. 1310-1322

Author(s):

Renata Zajaczkowska ◽

Klaudia Kwiatkowski ◽

Katarzyna Pawlik ◽

Anna Piotrowska ◽

Ewelina Rojewska ◽

...

Keyword(s):

Nervous System ◽

Neuropathic Pain ◽

Sciatic Nerve ◽

Nerve Injury ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Pain Treatment ◽

Opioid Analgesic ◽

Intraperitoneal Administration ◽

Pain Symptoms

Abstract Background Treatment of neuropathic pain is still challenging. Recent studies have suggested that dorsal root ganglia (DRG), which carry sensory neural signals from the peripheral nervous system to the central nervous system, are important for pathological nociception. A proper understanding of the significance and function of DRG and their role in pharmacotherapy can help to improve the treatment of neuropathic pain. Metamizole, also known as sulpyrine or dipyrone, is a non-opioid analgesic commonly used in clinical practice, but it is not used for neuropathic pain treatment. Methods Chronic constriction injury (CCI) of the sciatic nerve was induced in Wistar rats. Metamizole was administered intraperitoneally (ip) preemptively at 16 and 1 h before CCI and then twice a day for 7 days. To evaluate tactile and thermal hypersensitivity, von Frey and cold plate tests were conducted, respectively. Results Our behavioral results provide evidence that repeated intraperitoneal administration of metamizole diminishes the development of neuropathic pain symptoms in rats. Simultaneously, our findings provide evidence that metamizole diminishes the expression of pronociceptive interleukins (IL-1beta, IL-6, and IL-18) and chemokines (CCL2, CCL4, and CCL7) in DRG measured 7 days after sciatic nerve injury. These assays indicate, for the first time, that metamizole exerts antinociceptive effects on nerve injury-induced neuropathic pain at the DRG level. Conclusions Finally, we indicate that metamizole-induced analgesia in neuropathy is associated with silencing of a broad spectrum of cytokines in DRG. Our results also suggest that metamizole is likely to be an effective medication for neuropathic pain. Graphic abstract

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Opioid Analgesics in the Management of Neuropathic Pain

Pain Research and Management ◽

10.1155/2000/734239 ◽

2000 ◽

Vol 5 (1) ◽

pp. 89-91 ◽

Cited By ~ 1

Author(s):

Dwight Moulin

Keyword(s):

Neuropathic Pain ◽

Opioid Analgesic ◽

Opioid Analgesics ◽

Difficult Problem ◽

Physiochemical Properties ◽

Control Failure ◽

Unbearable Pain ◽

The Difference ◽

Higher Doses

The role of antidepressants and anticonvulsants in the management of neuropathic pain has been well established. However, up to 50% of patients obtain inadequate pain relief with the use of either or both of these agents; in this subpopulation, an opioid analgesic may be beneficial. There is clear evidence that opioid analgesics are efficacious in the management of neuropathic pain, but there is controversy as to the balance between analgesia and adverse effects. Opioid treatment may require higher doses than other kinds of drug therapies, thereby increasing the risk of opioid-related side effects. Psychological dependence or addiction, however, is not usually an issue in pain management with opioid analgesics. The extant literature strongly suggests the trial of an opioid analgesic in the management of neuropathic pain if adjuvant analgesics fail to provide adequate pain control. Failure of one opioid warrants a trial of another opioid because their effectiveness can vary among patients; the results are based on physiochemical properties of the drug and idiosyncratic reactions of the patient. Neuropathic pain can be a difficult problem to manage, and sometimes the use of an opioid analgesic can make the difference between bearable and unbearable pain so that patients can get on with their lives.

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The plasticity of the association between mu-opioid receptor and glutamate ionotropic receptor N in opioid analgesic tolerance and neuropathic pain

European Journal of Pharmacology ◽

10.1016/j.ejphar.2013.01.066 ◽

2013 ◽

Vol 716 (1-3) ◽

pp. 94-105 ◽

Cited By ~ 35

Author(s):

Pilar Sánchez-Blázquez ◽

Maria Rodríguez-Muñoz ◽

Esther Berrocoso ◽

Javier Garzón

Keyword(s):

Neuropathic Pain ◽

Opioid Receptor ◽

Opioid Analgesic ◽

Mu Opioid Receptor ◽

Ionotropic Receptor ◽

Analgesic Tolerance ◽

Mu Opioid

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New opioid analgesic tapentadol in the treatment of neuropathic pain in oncology

Medical Council ◽

10.21518/2079-701x-2019-10-180-184 ◽

2019 ◽

pp. 180-184

Author(s):

R. R. Sarmanaeva ◽

G. R. Abuzarova ◽

E. V. Gameeva

Keyword(s):

Neuropathic Pain ◽

Opioid Analgesic ◽

New Drugs ◽

Clinical Cases

Famous and familiar analgesics are being replaced by new drugs with improved properties. How to calculate their dose, in which category of patients to use, for what type of pain, with what dose to start therapy and with what adjuvants to combine? Many questions arise when a new opioid is being used. To answer these difficult questions, we decided to share our experience with the new analgesic tapentadol, describing real clinical cases from our practice.

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