Anatomy of pain can bring re­lief

Re­searchers are track­ing down how emo­tional in­puts mod­ify our ex­pe­ri­ence of pain, writes Stephen Pin­cock

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TOM had been in pain for close to a decade by the time he walked into Pro­fes­sor Michael Ni­cholas’s of­fice last year. What be­gan as a high school cricket in­jury — a stress frac­ture in his lower back — had led to nig­gling back pain that grad­u­ally wors­ened un­til he was of­ten in agony, only able to sit for a few min­utes at a time and un­able to walk fur­ther than 100 me­tres.

Tom was forced to quit full-time work, started re­ly­ing on a back brace and was ‘‘ pop­ping as many painkillers as I could’’ — all to no avail.

Sur­geons, os­teopaths, GPs and acupunc­tur­ists all told him much the same thing: the orig­i­nal in­jury had healed, so what was the prob­lem?

‘‘ They would all look at me and say ‘ There’s noth­ing wrong with you’,’’ re­calls Tom, who asked to with­hold his full name.

That changed when a sur­geon re­ferred Tom, now in his early 30s, to the Pain Man­age­ment and Re­search Cen­tre at Syd­ney’s Royal North Shore Hospi­tal. There, Pro­fes­sor Ni­cholas pre­scribed a com­bi­na­tion of phys­i­cal re­ha­bil­i­ta­tion and psy­cho­log­i­cal ther­apy. Tom be­gan to see im­me­di­ate ben­e­fits. ‘‘ Over the past 12 months or so, I’ve re­ally been able to learn to con­trol my pain,’’ he says. ‘‘ The most im­por­tant part of that is con­trol­ling the psy­cho­log­i­cal side of things.’’

An es­ti­mated one in five Aus­tralians suf­fers per­sis­tent pain, de­fined as pain that con­tin­ues for more than three months. Pre­cisely why it per­sists, some­times with­out any ob­vi­ous phys­i­cal cause, has re­mained some­thing of a mys­tery.

Now, Queens­land re­searchers have made a dis­cov­ery that sheds im­por­tant new light on how the brain pro­cesses pain, and how cen­tral emo­tions are in the pain ex­pe­ri­ence. Their work might lead to new treat­ments for chronic pain con­di­tions.

Andrew De­laney and his col­leagues at the Queens­land Brain In­sti­tute have pub­lished a study in the jour­nal Neu­ron about the in­tri­cate path­ways that are traced in the brain dur­ing the sen­sa­tion of pain (2007;56:880-892).

Us­ing a dye to la­bel neu­rons in rat brains, they were able to fol­low con­nec­tions be­tween the brain’s ‘‘ pain re­lay sta­tion’’, known as the parabrachial nu­cleus, and an­other brain re­gion known as the amyg­dala.

They found that nerve fi­bres from the pain re­lay sta­tion ran to spe­cific cells in the cen­tral part of the amyg­dala, form­ing what sci­en­tists call a ‘‘ high fi­delity con­nec­tion’’.

‘‘ That means that ev­ery time a neu­ron in the parabrachial nu­cleus ex­pe­ri­ences a pain in­put, the sig­nal is sent to the cen­tral amyg­dala. The high fi­delity con­nec­tion prac­ti­cally en­sures the cen­tral amyg­dala neu­ron fires as well,’’ De­laney ex­plains.

This very re­li­able con­nec­tion means that any sig­nal that reaches the brain’s pain cen­tre is al­most guar­an­teed to set off a sig­nal in the cen­tral amyg­dala. And the cells there trig­ger emo­tional re­sponses — emo­tions, hor­mones, blood pres­sure in­creases and so on.

From a clin­i­cal per­spec­tive, th­ese find­ings make a great deal of sense, says Pro­fes­sor Ni­cholas.

‘‘ Since the mid-1960s, we in the pain fra­ter­nity have seen pain as not sim­ply a sen­sa­tion, which is prob­a­bly how most of the com­mu­nity thinks of pain, but as be­ing de­fined by both a sen­sory and a emo­tional ex­pe­ri­ence,’’ he says.

‘‘ What trav­els through the nerves when you get an in­jury is not pain, it is ac­tiv­ity in nerves,’’ he ex­plains.

‘‘ We call that ‘ no­ci­cep­tion’. It’s only when it gets to the brain, and the brain syn­the­sises it and in­cor­po­rates a num­ber of other in­puts, that it be­comes an ex­pe­ri­ence of pain.’’

This is why peo­ple with chronic pain do so much bet­ter when they use psy­cho­log­i­cal strate­gies to help man­age their pain re­sponses, Ni­cholas says. And un­der­stand­ing the neu­ro­log­i­cal links be­tween pain and emo­tion is likely to help clar­ify just how the chronic pain de­vel­ops in the first place.

Pro­fes­sor MacDon­ald Christie, di­rec­tor of ba­sic re­search at the Pain Man­age­ment Re­search In­sti­tute at the Univer­sity of Syd­ney, says in the past five or six years it’s ‘‘ be­come in­creas­ingly clear that the trans­mis­sion of pain sig­nals from the spinal cord up through the parabrachial nu­cleus and into emo­tional con­trol sys­tems is a very im­por­tant com­po­nent of pain’’.

‘‘ The changes that oc­cur in that sys­tem in per­sis­tent pain states are ter­ri­bly im­por­tant for the es­tab­lish­ment of those states,’’ Christie says.

De­laney agrees. ‘‘ It could be that peo­ple who ex­pe­ri­ence chronic pain de­velop prob­lems be­cause they have dys­reg­u­la­tion of the pro­cess­ing in the amyg­dala, and of the pain in­put into the amyg­dala,’’ he says.

This is par­tic­u­larly likely be­cause the part of the amyg­dala the Queens­land group stud­ied also sends mes­sages di­rectly into the brain sys­tems that feed back to the spinal cord and con­trol pain sen­sa­tions.

Christie says this means that aber­ra­tions in the way the amyg­dala func­tions over time in chronic pain pa­tients ‘‘ will not only af­fect their anx­i­ety states, but also af­fect their ac­tual sen­sa­tion of pain and con­trib­ute to the es­tab­lish­ment of the chronic pain state’’.

Fur­ther, the Queens­land re­searchers also un­cov­ered a means by which the strong con­nec­tion be­tween the pain and emo­tion cen­tres in the brain can be in­ter­rupted.

They showed that a brain chem­i­cal called no­ra­drenaline, which is re­leased in sit­u­a­tions of stress or when we need to be on high alert, reg­u­lates the link.

‘‘ This seems to in­di­cate that dur­ing times of stress, our emo­tional re­sponse to pain may also be mod­u­lated, per­haps re­duc­ing the emo­tional im­pact of a painful ex­pe­ri­ence,’’ De­laney says.

Ni­cholas says this is ap­par­ent at times of high ex­cite­ment or stress, when peo­ple can some­times re­main un­aware they are in­jured at all, for a time.

‘‘ You can see that in foot­ballers when they come off the ground and dis­cover they’ve got a bro­ken nose they didn’t no­tice dur­ing the game,’’ says Ni­cholas.

‘‘ If you saw that foot­baller in the street and punched him in the nose, he’d cer­tainly recog­nise it as pain.’’

For pain re­searchers, un­der­stand­ing the role of no­ra­drenaline helps ex­plain why some of the drugs cur­rently used to treat pain ac­tu­ally work.

One ex­am­ple is the class of an­tide­pres­sant drugs known as no­ra­drenaline-re­up­take in­hibitors, such as re­box­e­tine.

‘‘ They al­low no­ra­drenaline to stay longer out­side cells to do its job,’’ De­laney says. ‘‘ By al­low­ing no­ra­drenaline to hang out a lit­tle longer, maybe you down-reg­u­late that re­sponse through your parabrachial to the cen­tral amyg­dala.’’

The find­ings could treat­ments.

‘‘ The new ev­i­dence we’ve got in this pa­per is that this is po­ten­tially one of those synapses where we may be able to use phar­ma­co­log­i­cal ther­apy to tar­get this part of pain,’’ says De­laney.

Al­though such new drugs could be years away, re­cent his­tory sug­gests the ba­sic science con­ducted in Bris­bane has a good chance of trans­lat­ing into ther­apy.

‘‘ There’s al­ready good re­cent his­tory of this sort of re­search trans­lat­ing very quickly into very use­ful ther­a­pies,’’ De­laney says.

‘‘ So we’d hope that not too far down the track we might have some­thing that would al­low us to tar­get the cells that re­ceive th­ese pain in­puts, or maybe tar­get the ter­mi­nals that re­lease the no­ra­drenaline to al­low them to be up­reg­u­lated.’’

For peo­ple like Tom and the many thou­sands of oth­ers with chronic pain, that would be wel­come news in­deed.





Pic­ture: David Sproule

Chan­nels of dis­cov­ery: Andrew De­laney’s re­search shows in­tri­cate path­ways are traced in the brain dur­ing an ex­pe­ri­ence of pain

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