Pathological pain and the neuroimmune interface

Pathological pain and the neuroimmune interface
Peter M. Grace, et al.
Nature Reviews Immunology  14, 217–231 (2014)

Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms.
Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells.

In this Review, we discuss the current understanding of the contribution of central immune mechanisms to pathological pain, and how the heterogeneous immune functions of different cells in the CNS could be harnessed to develop new therapeutics for pain control.

Given the prevalence of chronic pain and the incomplete efficacy of current drugs — which focus on suppressing aberrant neuronal activity — new strategies to manipulate neuroimmune pain transmission hold considerable promise.

Congenital insensitivity to pain

The Hazards of Growing Up Painlessly
Nov. 15, 2012

She can feel warmth and coolness, but not the more extreme temperatures that would cause anyone else to recoil in pain.

She can feel pressure and texture. She can feel a hug and a handshake. She felt her best friend, Katie, paint her toenails.

Dr. Roland Staud, a professor of medicine and rheumatologist at the University of Florida two mutations in her SCN9A gene.
That same gene, mutated in a different way, led to severe pain and chronic pain syndromes.

The connection between the gene and pain insensitivity was discovered in 2006 by a geneticist in Cambridge, England, named Geoffrey Woods.

Ashlyn’s mutation prevents the gene from making the channel, and the electrical impulses are never produced.

She could feel tickles and pressure and distinguish a soft touch from a pinprick, but she couldn’t perceive extremes of temperature.

she could feel emotional pain and empathy

Ashlyn does cry. She cried when her dog ran away earlier this year

She said that over the years she studied the expressions other people made and learned to cringe when someone described something painful.

“Define pain for you,” John said. “What does it mean for you?”
“I don’t know.”
“When you see someone else in pain, what do you associate?”
“That must really hurt.”
“What is hurt?”
Ashlyn squinted her eyes, as if in deep thought.
She couldn’t answer him.

unintentionally self-destructive children

Some of the children who came to the camp had a mutation on a gene, NTRK1, that is involved in the development and maturation of the nervous system and that is characterized by self-mutilating behavior, fevers, mental retardation along with insensitivity to pain.

Hereditary sensory and autonomic neuropathy
Type 2, Congenital sensory neuropathy
Type 4, Congenital insensitivity to pain with anhidrosis
Type 5, Congenital insensitivity to pain with partial anhidrosis

Congenital Insensitivity to pain

When Math Hurts: Math Anxiety Predicts Pain Network Activation in Anticipation of Doing Math

When Math Hurts: Math Anxiety Predicts Pain Network Activation in Anticipation of Doing Math
October 31, 2012