Contribution of primary afferent channels to neuropathic pain

Harriott, Andrea M.; Gold, Michael S.

doi:10.1007/s11916-009-0034-9

Cited by 47 publications

(35 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is increasing evidence from molecular biological and biophysical studies that primary afferent neurons contain unique proteins that can subserve the transduction of thermal (heating and cooling), mechanical and chemical stimuli 32 (Fig. 1 and Table 1).…”

Section: Mechanisms Of Transductionmentioning

confidence: 99%

Nociceptor sensitization in pain pathogenesis

Gold

Gebhart

2010

Nat Med

708

625

View full text Add to dashboard Cite

The incidence of chronic pain is estimated to be 20–25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of the heterogeneity of mechanisms that contribute to the transition from acute tissue insult to chronic pain and to pain conditions for which the underlying pathology is not apparent. An intact central nervous system (CNS) is required for the conscious perception of pain, and changes in the CNS are clearly evident in chronic pain states. However, the blockage of nociceptive input into the CNS can effectively relieve or markedly attenuate discomfort and pain, revealing the importance of ongoing peripheral input to the maintenance of chronic pain. Accordingly, we focus here on nociceptors: their excitability, their heterogeneity and their role in initiating and maintaining pain.

show abstract

Section: Mechanisms Of Transductionmentioning

confidence: 99%

Nociceptor sensitization in pain pathogenesis

Gold

Gebhart

2010

Nat Med

708

625

View full text Add to dashboard Cite

show abstract

“…Depending on the subtypes of sensory fibres involved, this can lead to diverse symptoms such as mechanical and thermal pain hypersensitivity [24]. For example, vesicular glutamate transporter 3 positive (VGluT3 + ) sensory fibres do not mediate pain in naïve animals or heat hypersensitivity after injury, but are involved in mechanical and cold hypersensitivity in some animal models of neuropathic and inflammatory pain [13;44].…”

Section: Introductionmentioning

confidence: 99%

Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by opioids and baclofen

Honsek

Seal

Sandkühler

2015

Pain

View full text Add to dashboard Cite

Distinct subsets of sensory nerve fibres are involved in mediating mechanical and thermal pain hypersensitivity. They may also differentially respond to analgesics. Heat-sensitive C-fibres, for example, are thought to respond to µ-opioid receptor (MOR) activation while mechanoreceptive fibres are supposedly sensitive to δ-opioid receptor (DOR) or GABAB receptor (GABABR) activation. The suggested differential distribution of inhibitory neurotransmitter receptors on different subsets of sensory fibres is, however, heavily debated. We now quantitatively compared the degree of presynaptic inhibition exerted by opioids and the GABABR agonist baclofen on 1) vesicular glutamate transporter subtype 3 positive (VGluT3+) non-nociceptive primary afferent fibres and 2) putative nociceptive C-fibres. To investigate VGluT3+ sensory fibres, we evoked excitatory postsynaptic currents with blue light at the level of the dorsal root ganglion (DRG) in spinal cord slices of mice, expressing channelrhodopsin-2. Putative nociceptive C-fibres were explored in VGluT3-knockout mice via electrical stimulation. The MOR agonist DAMGO strongly inhibited both VGluT3+ and VGluT3− C-fibres innervating lamina I neurons but generally had less influence on fibres innervating lamina II neurons. The DOR agonist SNC80 did not have any pronounced effect on synaptic transmission in any fibre type tested. Baclofen, in striking contrast, powerfully inhibited all fibre populations investigated. In summary, we report optogenetic stimulation of DRG neurons in spinal slices as capable approach for the subtype-selective investigation of primary afferent nerve fibres. Overall, the pharmacological accessibility of different subtypes of sensory fibres considerably overlaps, indicating that MOR, DOR and GABABR expression is not substantially segregated between heat and mechanosensitive fibres.

show abstract

“…Unlike inflammatory pain, underlying molecular mechanisms of neuropathic pain remains poorly understood (Harriott and Gold, 2009). One of the main reasons might be the heterogeneity of etiological origins.…”

Section: Neuropathic Painmentioning

confidence: 99%

Section: Neuropathic Painmentioning

confidence: 99%

“…Central changes may influence the intensity and quality but seem insufficient for the overt manifestation of neuropathic pain (Dubner, 2004;Harriott and Gold, 2009). It is currently assumed that spontaneous activity in neuropathic pain reflects the ongoing activation of a subset of nociceptive afferents and/or nonnociceptive neuron that switch their phenotype as a consequence of the lesion (Harriott and Gold, 2009). The driving force underlying this activity is derived from a combination of terminal sensitization (Campbell and Meyer, 2006), the upregulation of ion channels such as Na v 1.3 (Waxman et al, 1994) or HCN channels (Jiang et al, 2008) and the increase of action potential generation in the central projections of nociceptors (dorsal root reflex) (Willis, 1999).…”

Section: Neuropathic Painmentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneity in primary nociceptive neurons: From molecules to pathology

Gascon

Moqrich

2010

Arch. Pharm. Res.

View full text Add to dashboard Cite

Pain sensation (nociception) is an alarm system aiming to signal the presence of potentially or actually harmful stimuli. In our hazard-rich environment, pain initiates the necessary reactions to prevent or limit tissue damage in response to noxious inputs playing therefore a crucial survival role. Specialized noxious stimuli detectors, called primary nociceptive neurons or nociceptors transduce and convey pain information to the central nervous system. Unlike other sensory systems, pain sensation could be evoked by a vast range of external or internal stimuli. Nearly any of the environmental stimuli could be potentially noxious depending on their nature and/or intensity and/or duration. Early studies at the beginning of the 20th century identified a discrete number of nociceptive neuronal types according to their electrophysiological responses or their degree of myelination. However, the advent of molecular biology techniques revealed an extraordinary diversity among nociceptors. Such heterogeneity likely reflects the evolutionary adaptation required to respond to an extremely variety of circumstances.

show abstract

Contribution of primary afferent channels to neuropathic pain

Cited by 47 publications

References 62 publications

Nociceptor sensitization in pain pathogenesis

Nociceptor sensitization in pain pathogenesis

Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by opioids and baclofen

Heterogeneity in primary nociceptive neurons: From molecules to pathology

Contact Info

Product

Resources

About