Gene therapy for pancreatitis pain

Westlund, Karin N.

doi:10.1038/gt.2009.27

Cited by 17 publications

(10 citation statements)

References 76 publications

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“…The expression pattern was similar in the DRG and in the spinal cord, the only difference being the lack of statistical significance in the differences between KO and WT mice regarding ENK and SP in the spinal cord. Usually, CGRP acts as a promoter of pain sensitivity (13), whereas ENK has analgesic properties (14); therefore, our expression studies suggest that the KO mice should present a lower threshold for pain sensitivity. This is in agreement with our hotplate results, although the tail-flick experiments showed something different, indicating the existence of further layers of complexity in the involvement of AM in the processing of pain sensitivity (see below).…”

Section: Discussionmentioning

confidence: 97%

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

et al. 2010

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Adrenomedullin (AM) is a regulatory peptide, coded by the adm gene, which is involved in numerous physiological processes, including pain sensitivity. Previous studies have shown that intrathecal injection of AM induced hyperalgesia in the rat. Here, we explore pain sensitivity in a mouse conditional knockout for adm in neurons of the central nervous system, including the spinal cord and dorsal root ganglia. Double immunofluorescence in wild-type (WT) animals shows that AM immunoreactivity is found in calcitonin gene-related peptide-positive neurons of the dorsal root ganglia but not in neurons that bind isolectin B4. Mice lacking adm had modified expression of canonical sensorial neuropeptides, having significantly more calcitonin gene-related peptide and less substance P and enkephalin than their WT littermates. Furthermore, the spinal cord of adm knockout mice expressed higher levels of the AM receptor components, suggesting a compensation attempt to deal with the lack of afferent AM signaling. Behavioral nociceptive tests also found differences between genotypes. In the tail-flick test, which measures mostly spinal reflexes, the adm-null animals had a longer latency than their WT counterparts. On the other hand, in the hotplate test, which requires encephalic processing, mice lacking adm had shorter latencies than normal littermates. These results suggest that AM acts as a nociceptive modulator in spinal reflexes, whereas it may have an analgesic function at higher cognitive levels. This study confirms the important role of AM in pain sensitivity processing but unveils a more complex scenario than previously surmised.

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Section: Discussionmentioning

confidence: 97%

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

et al. 2010

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“…were also reduced (Lu et al, 2007). The insights gained from this model may lead to new, innovative gene therapy approaches designed specifically to treat this type of pain (Westlund, 2009). …”

Section: Pancreatitis Modelmentioning

confidence: 96%

Neurobiological studies of chronic pain and analgesia: Rationale and refinements

Fairbanks

Goracke-Postle

2015

European Journal of Pharmacology

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“…In initial fMRI studies using the acute DBTC induced pancreatitis model, we determined l e v e l s o f n e u r o n a l a c t i v a t i o n i n h i g h e r b r ain centers along the visceral pain pathway (Westlund, 2000) finding significant activation in rostral ventrolateral medulla, dorsal raphe, periaqueductal grey, medial thalamus and central amygdala in rats (Westlund et al, 2009). …”

Section: Opiate Gene Therapy Studiesmentioning

confidence: 99%

Gene Therapy Approach: HSV-Enkephalin Reduces Fibrosis, Inflammation, and Pain

Westlund¹

2012

Chronic Pancreatitis

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Gene therapy for pancreatitis pain

Cited by 17 publications

References 76 publications

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

Neurobiological studies of chronic pain and analgesia: Rationale and refinements

Gene Therapy Approach: HSV-Enkephalin Reduces Fibrosis, Inflammation, and Pain

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