Highlights • Quinpirole alleviates cold and tactile allodynia in a rat model of neuropathic pain. • Spinal mechanisms might be involved in the anti-allodynic effect of quinpirole. • However, ...supraspinal mechanisms probably account for most of the analgesic activity. • Pain relief is gradually achieved when quinpirole in chronically administered. • The study shows the potential of D2R agonists for the management of neuropathic pain.
Subarachnoidal grafting of monoamine-producing cells has been used with success to treat chronic pain in animal models. In the search for a source of autologous transplantable cells, capable of ...delivering neuroactive substances to the cerebrospinal fluid (CSF) to treat pain, we have tested adipose tissue-derived stromal cells (ADSCs) transduced to produce levodopa. Intrathecally grafted ADSCs survive for long term adhered to spinal cord and nerve root meninges. Cultured ADSCs were retrovirally transduced with tyrosine hydroxylase (TH) and/or GTP cyclohydroxylase 1 (GCH1) genes and stably expressed them for at least 6 weeks in culture. Singly transduced cultures did not produce measurable levodopa but doubly transduced or a mixture of singly transduced ADSCs were able to efficiently synthesize and release levodopa. When 0.5–1 × 106 TH-and GCH1-expressing ADSCs were intrathecally grafted in rats, elevated levels of levodopa and dopamine metabolites were found in CSF at 3 days, although at lower concentrations than expected. Unexpectedly, no levodopa was measurable in CSF at 6 days. In a rat model of neuropathic pain, intrathecal grafting of doubly transduced cells did not produce antiallodynic effects at 2 or 6 days, even when histological analysis revealed the presence of weak TH-immunoreactive subarachnoidal cell clusters. These results suggested that doubly transduced cells could indeed function as biological minipumps to enhance the dopaminergic neurotransmission at the spinal cord level but transgenes were rapidly silenced after intrathecal grafting. Transgene silencing was mimicked in culture by serum deprivation for 3 days. Serum addition at this point recovered trans-gene expression in just 6 h, as did, to a smaller degree, dbcAMP or histone deacetylase inhibitors. Transgene expression silencing in serum deprivation conditions was prevented by 5′-terminal IRES sequences. The present study does not discard the use of transduced cells as a strategy to treat chronic pain but shows that controlling transgene silencing in implanted cells needs to be achieved first.
Abstract Levodopa has been shown to produce analgesia in various clinical and experimental settings, but its use for chronic pain treatment has not been established. We have undertaken a study of the ...antiallodynic actions of levodopa in a rat model of painful mononeuropathy. When administered systemically, levodopa produced a decrease in tactile and cold allodynia lasting at least 3 h. Direct intrathecal (i.t.) levodopa injection at lumbar levels produced a similar, though shorter, antiallodynic effect. This effect was blocked by the D2-type receptor antagonist sulpiride, which supports the involvement of the spinal dopaminergic system in the analgesic action of levodopa on neuropathic pain. These results provide experimental support on the antiallodynic effect of levodopa in neuropathic pain and suggest that at least part of the analgesic action takes place in the spinal cord and involves dopaminergic D2-type receptors.
The overgrowth and shading of several alien species along the European Atlantic coast are expected to reduce photosynthesis of maerl, decreasing its growth and fitness. In this work, three shade ...levels (0, 20 and 50%) were set up under laboratory conditions to simulate different competitive scenarios potentially affecting maerl beds. Live individuals of
and
were placed over maerl cultures, and the effects of shading were assessed by chlorophyll
fluorescence using a pulse-modulated fluorescence monitoring system. Photosystem II efficiency was measured as the ratio of variable to maximal fluorescence (F
/F
) as a proxy for the stress experienced by maerl. According to our data, irradiance reduction results in a small, yet significant, impact on the PSII efficiency of maerl, which could have fitness consequences.
