Gene gun particle encoding preproenkephalin cDNA produces analgesia against capsaicin-induced bladder pain in rats

Chuang, Yao‐Chi; Yang, Lin-Cheng; Chiang, Po‐Hui; Kang, Hong-Yo; Lung, Wen; Wu, Ping; DeMiguel, Fernando; Chancellor, Michael B.; Yoshimura, Naoki

doi:10.1016/j.urology.2004.10.070

Cited by 20 publications

(16 citation statements)

References 20 publications

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“…This is much shorter than the effects measured for 2-20 weeks after injections of viral vectors encoding opioid peptides [5,7-14,16], or up to 2 weeks after endomorphin-2-HSV or POMC plasmid applications [14,20,23]. However, in other studies using END-coding adenoviral vector or POMC plasmids, attenuation of hyperalgesia was only measured in short-lasting (30 min-3 h) pain models [15,18,19,21,22]. Thus, longer-lasting anti-hyperalgesic effects were mostly produced by viral vectors preferentially targeting neurons [5,7-14,16].…”

Section: Discussionmentioning

confidence: 99%

Peripheral Non-Viral MIDGE Vector-Driven Delivery of β-Endorphin in Inflammatory Pain

et al. 2009

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BackgroundLeukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, anti-bacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE) vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS)-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC) on complete Freund's adjuvant-induced inflammatory pain in rats.ResultsPOMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin.ConclusionAlthough MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.

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Section: Discussionmentioning

confidence: 99%

Peripheral Non-Viral MIDGE Vector-Driven Delivery of β-Endorphin in Inflammatory Pain

et al. 2009

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“…showed that nNOS gene transfer led to an increase in NO production within the bladder smooth muscle layer. Finally, gene gun delivery of gold particle-linked DNA (Figure 2) to the bladders of animals in which the bladder has been exposed by a midline incision enabled delivery of molecules that alter the painful responses to bladder nociceptive stimuli in animal models of cystitis127,128 discussed in detail below.…”

Section: Gene Therapy: An Alternative Therapy For Lut Painmentioning

confidence: 99%

“…Toward this goal, non-viral vectors using the gene gun technology to transfer either the pro-opiomelanocortin127 or preproenkephalin (PPE)128 expression cassette plasmid DNAs linked to gold particles into the bladder of rats where the bladder is exposed by a low midline incision were employed in cystitis models. Cystometric measurements in rats receiving pro-opiomelanocortin gold particles127 showed an increased ICI compared with control animals following the infusion of 0.3% acetic acid irritant into the bladder at 3 days after the introduction of three gold particle-DNA bullets into three sites within the bladder wall (Figure 3a), which correlated with β-endorphin expression within the bladder.…”

Section: Gene Therapy: An Alternative Therapy For Lut Painmentioning

confidence: 99%

“…Moreover, the specificity of the response could be reversed by treatment of these animals with opioid receptor antagonist naloxone hydrochloride. In an attempt to block δ-rather than μ-opioid receptor pain signaling, PPE plasmid DNA linked to gold particles were employed in a similar cystitis model except that 15 μM capsaicin was used as a bladder irritant instead of acetic acid 128. As seen earlier, opioid gene expression at 4–7 days postinjection resulted in a lessening of the effects of capsaicin of δ-opioid receptor activation/signaling that again was specifically blocked by naloxone HCI (Figure 3b).…”

Section: Gene Therapy: An Alternative Therapy For Lut Painmentioning

confidence: 99%

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Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain

et al. 2009

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Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance; therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virusdirected delivery of analgesic proteins to the bladder.

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“…Scientists are searching for methods to prolong the gene expression induced by gene gun therapy, such as repeated gene gun treatments or other novel modifications of the technology to prolong its effect. Regardless, this is a potentially exciting approach to another condition with few effective treatment options [32].…”

Section: Gene Therapy With Endogenous Opioids To Treat Painful Bladdementioning

confidence: 99%

An update on gene therapy/transfer treatments for bladder dysfunction

Christ

Hodges

Melman

2006

Curr Bladder Dysfunct Rep

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Gene gun particle encoding preproenkephalin cDNA produces analgesia against capsaicin-induced bladder pain in rats

Cited by 20 publications

References 20 publications

Peripheral Non-Viral MIDGE Vector-Driven Delivery of β-Endorphin in Inflammatory Pain

Peripheral Non-Viral MIDGE Vector-Driven Delivery of β-Endorphin in Inflammatory Pain

Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain

An update on gene therapy/transfer treatments for bladder dysfunction

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