Targeting cytokines for treatment of neuropathic pain

Hung, Alice L.; Lim, Michael; Doshi, Tina L.

doi:10.1016/j.sjpain.2017.08.002

Cited by 140 publications

(136 citation statements)

References 119 publications

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“…Many studies have demonstrated that pain behaviors can be attenuated by local or spinal administration of agents that antagonize TNF-α (105)(106)(107)(108). TNF soluble receptor (TNFSR), commercially known as etanercept, is previously approved by the FDA for treatment of painful inflammatory conditions including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis (109). While preclinical trials with recombinant TNFSR have shown promise, randomized clinical trials have had limited success (109).…”

Section: Tumor Necrosis Factor and Pathological Painmentioning

confidence: 99%

“…TNF soluble receptor (TNFSR), commercially known as etanercept, is previously approved by the FDA for treatment of painful inflammatory conditions including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis (109). While preclinical trials with recombinant TNFSR have shown promise, randomized clinical trials have had limited success (109). Clinical translation may be limited by the potential loss of beneficial neuroprotective and neuroregenerative properties of TNF-α, and by its impermeability at the blood-brain-barrier (9).…”

Section: Tumor Necrosis Factor and Pathological Painmentioning

confidence: 99%

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Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

2019

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Current pain therapeutics offer inadequate relief to patients with chronic pain. A growing literature supports that pro-inflammatory cytokine signaling between immune, glial, and neural cells is integral to the development of pathological pain. Modulation of these communications may hold the key to improved pain management. In this review we first offer an overview of the relationships between pro-inflammatory cytokine and chemokine signaling and pathological pain, with a focus on the actions of cytokines and chemokines in communication between glia (astrocytes and microglia), immune cells (macrophages and T cells), and neurons. These interactions will be discussed in relation to both peripheral and central nervous system locations. Several novel non-neuronal drug targets for controlling pain are emerging as highly promising, including non-viral IL-10 gene therapy, which offer the potential for substantial pain relief through localized modulation of targeted cytokine pathways. Preclinical investigation of the mechanisms underlying the success of IL-10 gene therapy revealed the unexpected discovery of the powerful anti-nociceptive anti-inflammatory properties of D-mannose, an adjuvant in the non-viral gene therapeutic formulation. This review will include gene therapeutic approaches showing the most promise in controlling pro-inflammatory signaling via increased expression of anti-inflammatory cytokines like interleukin-10 (IL-10) or IL-4, or by directly limiting the bioavailability of specific pro-inflammatory cytokines, as with tumor necrosis factor (TNF) by the TNF soluble receptor (TNFSR). Approaches that increase endogenous anti-inflammatory signaling may offer additional opportunities for pain therapeutic development in patients not candidates for gene therapy. Promising novel avenues discussed here include the disruption of lymphocyte function-associated antigen (LFA-1) activity, antagonism at the cannabinoid 2 receptor (CB2R), and toll-like receptor 4 (TLR4) antagonism. Given the partial efficacy of current drugs, new strategies to manipulate neuroimmune and cytokine interactions hold considerable promise.

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Section: Tumor Necrosis Factor and Pathological Painmentioning

confidence: 99%

Section: Tumor Necrosis Factor and Pathological Painmentioning

confidence: 99%

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

2019

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“…interleukin‐1 β (IL‐1 β ), IL‐18, IL‐6 and nitric oxide synthase 2 (NOS2)] and antinociceptive factors [e.g. IL‐1 receptor antagonist (IL‐1RA), IL‐18 binding protein (IL‐18BP) and IL‐10] contributes to the development of neuropathic pain . Moreover, research on chemokines has suggested that their systems (ligands/receptors) are involved in pathological nociceptive processes .…”

Section: Introductionmentioning

confidence: 99%

“…IL-1 receptor antagonist (IL-1RA), IL-18 binding protein (IL-18BP) and IL-10] contributes to the development of neuropathic pain. [6][7][8][9] Moreover, research on chemokines has suggested that their systems (ligands/receptors) are involved in pathological nociceptive processes. [10][11][12] Our recent results indicated that the blockade of some chemokine receptors (e.g.…”

Section: Introductionmentioning

confidence: 99%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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Summary A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up‐regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA‐1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin‐1β (IL‐1β), IL‐6 and IL‐18. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid‐induced analgesia through the modulation of neuroimmune interactions.

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“…A previous study showed that lncRNA Musmusculus predicted gene 14,461 (Gm14461) was highly expressed in injured DRG 6 days after spinal nerve ligation in mice with neuropathic pain, suggesting that Gm14461 may be involved in regulating neuropathic pain [11]. Diverse causes of neuropathic pain are associated with excessive inflammation [12,13]. Cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 play a very important role in the pathogenesis of TN by regulating the immune response within the peripheral endings of trigeminal ganglion neurons (TGNs) [14].…”

Section: Introductionmentioning

confidence: 99%

Effects of long non-coding RNA Gm14461 on pain transmission in trigeminal neuralgia

Yan

Zhu

et al. 2020

J Inflamm

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Background: This study aims to investigate the role of long non-coding RNA Gm14461 in regulating pain transmission in trigeminal neuralgia (TN). The mouse TN model was produced by chronic constriction injury of the infraorbital nerve (CCI-ION). The values of mechanical withdrawal threshold (MWT) were measured to assess the nociception of mice at different times after CCI-ION surgery (0, 1, 3, 5, 7, 9, 11, 13, 15 d). The primary mouse trigeminal ganglion neurons (TGNs) were isolated from C57BL/6 J mice and treated with TNF-α to mimic a TN cellular model. The expression of Gm14461, TNF-α, IL-1β, and IL-6 was examined using qRT-PCR. The protein levels of CGRP and P2X3/7 receptor were measured using western blot.Results: Gm14461 expression was increased in trigeminal ganglia (TGs) of TN mice on the operation side. Furthermore, Gm14461 knockdown in TGs increased, whereas Gm14461 overexpression decreased MWT in TN mice. Moreover, Gm14461 knockdown downregulated, whereas Gm14461 overexpression upregulated mRNA levels of TNF-α, IL-1β, and IL-6 and protein levels of CGRP and P2X3/7 receptor in TGs from TN mice. In vitro assay showed that Gm14461 was upregulated by TNF-α, IL-1β, and IL-6. Additionally, Gm14461 knockdown decreased protein levels of CGRP and P2X3/7 receptor in TNF-α-treated TGNs, whereas Gm14461 overexpression exerted the opposite effect.Conclusion: Gm14461 promoted pain transmission (reduced MWT value) in a CCI-ION-induced mouse TN model. The underlying mechanisms might involve the regulation of pro-inflammatory cytokines, CGRP and P2X3/7 receptor.

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Targeting cytokines for treatment of neuropathic pain

Cited by 140 publications

References 119 publications

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

Effects of long non-coding RNA Gm14461 on pain transmission in trigeminal neuralgia

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