Central sensitization in medullary dorsal horn involves gap junctions and hemichannels

  title={Central sensitization in medullary dorsal horn involves gap junctions and hemichannels},
  author={Chen Yu Chiang and Zhaohui Li and Jonathan O. Dostrovsky and Barry John Sessle},
Central sensitization is a fundamental mechanism contributing to acute and chronic pain conditions. Our previous studies have documented a glutamatergic, purinergic and glial-dependent central sensitization that can be induced in rat medullary dorsal horn nociceptive neurons by mustard oil application to the tooth pulp. This study showed that carbenoxolone, a potent gap junction and hemichannel blocker, completely blocked all parameters of mustard oil-induced central sensitization tested in… 

Trigeminal Central Sensitization and Its Modulation in Acute and Chronic Orofacial Pain Models

Findings reveal that MDH CS occurs in mouse models of acute and chronic orofacial pain and that pregabalin may prove useful clinically in acute and Chronic oroFacial pain states.

Role of gap junctions in chronic pain

This Mini‐Review highlights recent studies demonstrating the dynamic plasticity of gap junctions in response to nervous system injury and the effects of gap junction blockade on neuronal survival and modulation of pain in animal models of neuropathic and inflammatory pain.

Modulation of astroglial glutamine synthetase activity affects nociceptive behaviour and central sensitization of medullary dorsal horn nociceptive neurons in a rat model of chronic pulpitis

Behavioural and neuronal findings suggest that the astroglial glutamate–glutamine shuttle is responsible for the maintenance of inflammation‐induced nocifensive behavioural changes and the accompanying central sensitization in MDH nociceptive neurons in this chronic pulpitis pain model.

Neuron–Glia Crosstalk and Neuropathic Pain: Involvement in the Modulation of Motor Activity in the Orofacial Region

Neuron–glia crosstalk plays an important role in the development of pain and altered motor activity in NOP and an involvement of the astroglial glutamate–glutamine shuttle in the trigeminal motor nucleus in the alteration of the jaw reflex is found.

Role of Astrocytes in Pain

The interactions between astrocytes, microglia and neurons are now recognized as fundamental mechanisms underlying acute and chronic pain states.

Spinal astrocyte gap junctions contribute to oxaliplatin-induced mechanical hypersensitivity.

Central sensitization: Implications for the diagnosis and treatment of pain



Glutamine uptake contributes to central sensitization in the medullary dorsal horn

It is found that superfusion onto MDH of methylaminoisobutyric acid, a competitive inhibitor of the neuronal system A transporter for presynaptic uptake of glutamine, significantly depressed development of mustard oil-induced central sensitization in rat MDH nociceptive neurons.

Endogenous ATP involvement in mustard-oil-induced central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn).

The findings implicate endogenous ATP as an important mediator contributing to the development of central sensitization in nociceptive neurons of the deep laminae of the dorsal horn.

Astroglial Glutamate–Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn

It is demonstrated that the central sensitization induced in functionally identified nociceptive neurons in trigeminal subnucleus caudalis (the medullary dorsal horn) by application of an inflammatory irritant to the rat's tooth pulp can be significantly attenuated by continuous intrathecal superfusion of methionine sulfoximine.

Cellular neuroplasticity mechanisms mediating pain persistence.

  • M. Salter
  • Biology
    Journal of orofacial pain
  • 2004
Persistent enhancement of nociceptive transmission, known as "central sensitization," is a form of lasting plasticity that is similar mechanistically to long-term potentiation of glutamatergic transmission in other regions of the central nervous system.

Direct actions of carbenoxolone on synaptic transmission and neuronal membrane properties.

The results indicate CBX broadly affects several neuronal membrane conductances independent of its effects on gap junctions, indicating effects of carbenoxolone on network activity cannot be interpreted as resulting from specific block of gap junction junctions.

Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration.

Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases.

Pharmacological “cross‐inhibition” of connexin hemichannels and swelling activated anion channels

Carbenoxolone (CBX), the most widely used gap junction/hemichannel blocker, was an effective blocker of VRAC‐mediated glutamate and taurine release, and blocked these channels at similar concentrations at which it blocked hemichannels.

Gap junction hemichannels in astrocytes of the CNS.

Hemichannels constituted of Cx43, the main connexin expressed by astrocytes, are permeable to small physiologically significant molecules, such as ATP, NAD+ and glutamate, and may mediate paracrine as well as autocrine signalling.

Carbenoxolone inhibits volume-regulated anion conductance in cultured rat cortical astroglia

Findings support the notion that CBX could affect astroglial ability to modulate neuronal activity by suppressing excitatory amino acid release through VRAC, and provide a possible mechanistic clue for the neuroprotective effect of CBX in vivo.