Supraspinal Glial–Neuronal Interactions Contribute to Descending Pain Facilitation

Minocycline modulates neuropathic pain behaviour and cortical M1–M2 microglial gene expression in a rat model of depression

“…Furthermore, minocycline has been shown to be beneficial in pain states such as rheumatoid arthritis (Langevitz et al, 2000) and sciatica (Sumracki et al, 2012). Both systemic and central administration of minocycline has been shown to prevent microglial activation and release of pro-inflammatory cytokines/mediators, and consequently the development of nerve injury-induced allodynia in several models (Raghavendra et al, 2003, Zanjani et al, 2006, Guasti et al, 2009, Pu et al, 2013, LeBlanc et al, 2011, Wei et al, 2008.…”

Medication-overuse headache and opioid-induced hyperalgesia: A review of mechanisms, a neuroimmune hypothesis and a novel approach to treatment

“…[94][95][96] Activation of spinal microglia and astrocytes has been demonstrated in virtually every clinically relevant animal model of an enhanced pain state 88 with similar results reported for trigeminal pain models. 97 Moreover, glial-attenuating pharmacological interventions are able to block the phenotypic transformation of glial cells into the activated state and prevent both allodynia and hyperalgesia across a diverse range of pre-clinical pathological pain models. [98][99][100][101][102][103] It is now clear that glia-to-neuron signaling via toll-like receptor 4 (TLR-4) can play a causal role in the initiation and maintenance of pathological pain.…”

Glial Modulation of Pain: A Step Beyond: Figure 1.

“…In a recent study published in The Journal of Neuroscience, Wei et al (2008) further explored the contribution of neuron-glia interactions in the genesis of neuropathic pain by investigating whether this cross talk occurs in areas of the CNS beyond the spinal cord and trigeminal nucleus. Using a model of peripheral lesion of the infraorbital nerve, which produces severe and long-lasting pain-related behaviors [Wei et al (2008), their Fig.…”

“…Using a model of peripheral lesion of the infraorbital nerve, which produces severe and long-lasting pain-related behaviors [Wei et al (2008), their Fig. 1 (http://www.jneurosci.org/ cgi/content/full/28/42/10482/F1)], the authors observed an increase in the expression of specific markers of astrocyte (GFAP and S110␤) and microglia (CD11 and Iba1) activation in RVM [Wei et al (2008) To investigate the functionality of this activation, Wei et al (2008) asked whether glial cell activation participates in the cascade of events leading to pain behavior induced by peripheral nerve lesion. Selectively inhibiting activation of microglia (by minocycline) or astrocytes (by fluorocitrate), or nonselectively inhibiting activation of both (by propentofylline) transiently suppressed pain-related behaviors induced by peripheral nerve lesion [Wei et al (2008), their Fig.…”

“…While it is not determined, there are many options based on the following evidence: (1) glutamate; intra-RVM administration of a NMDA receptor antagonist (MK-801) reduces neuropathic pain; the activation of glial cells in the spinal cord during a neuropathic process is also blocked by intrathecal MK-801 (Wei and Pertovaara, 1999;Watkins and Maier, 2002); (2) cholecystokinin (CCK); CCK B receptor antagonist into RVM also reduced neuropathic pain (Kovelowski et al, 2000); (3) ATP; several ATP purinergic receptors are detected in RVM, and direct application of ATP in this area modulates the activity of a subclass of neurons (Selden et al, 2007); (4) substance P (SP); NK-1 receptor located in RVM contributes to hyperalgesia induced by capsaicin (Pacharinsak et al, 2008); SP is also implicated in peripheral nerve lesion-induced glial cell activation in the spinal cord (Watkins and Maier, 2002); and (5) fractalkine; CX3CR1 receptor is constitutively expressed in RVM, and fractalkine is a well known activator of microglia in the spinal cord during neuropathies (Watkins and Maier, 2002;Zhang et al, 2008). Wei et al (2008) found that activation of microglia and astrocytes had different time courses. Whereas microglia were activated at 3 d after injury, astrocyte activation was not observed until 14 d after nerve damage.…”